A bi-functional hepatitis B virus core antigen (HBcAg) chimera activates HBcAg-specific T cells and preS1-specific antibodies

A major problem in chronic hepatitis B virus (HBV) infection is that treatment with specific antivirals is life-long since they rarely induce a sustained response. An attractive option is therefore to combine antiviral therapy with some type of immune stimulator, such as a therapeutic vaccine. Several lines of evidence suggest that a key target for the cellular immune response is the HBV core antigen (HBcAg). However, it may also be of advantage to simultaneously improve the neutralizing antibody response to the surface (S) region of HBV. We therefore generated chimeric HBcAg particles expressing preS1 residues 1-42 at the tip of the spike region. We could show that this chimeric HBcAg-preS1 protein primed both HBcAg-specific T cells and antibodies to preS1. This strongly suggests that this may be a viable approach to develop an effective bi-functional therapeutic vaccine as an add-on for the treatment of chronic HBV infections.     

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.     

The formation of an organic coat and the release of corrosion microparticles from metallic magnesium implants

Magnesium alloys have been proposed as prospective degradable implant materials. To elucidate the complex interactions between the corroding implants and the tissue, magnesium implants were analyzed in a mouse model and the response was compared to that induced by Ti and by the resorbable polymer polyglactin, respectively. One month after implantation, distinct traces of corrosion were apparent but the magnesium implants were still intact, whereas resorbable polymeric wound suture implants were already fragmented. Analysis of magnesium implants 2 weeks after implantation by energy-dispersive X-ray spectroscopy indicated that magnesium, oxygen, calcium and phosphate were present at the implant surface. One month after implantation, the element composition of the outermost layer of the implant was indicative of tissue without detectable levels of magnesium, indicating a protective barrier function of this organic layer. In agreement with this notion, gene expression patterns in the surrounding tissue were highly similar for all implant materials investigated. However, high-resolution imaging using energy-filtered transmission electron microscopy revealed magnesium-containing microparticles in the tissue in the proximity of the implant. The release of such corrosion particles may contribute to the accumulation of calcium phosphate in the nearby tissue and to bone conductive activities of magnesium implants.     

Irreversible delayed complete heart block secondary to jailed first septal perforator following PCI of the left anterior descending coronary artery

Permanent complete heart block (CHB) secondary to the loss of first septal perforator after percutaneous coronary intervention (PCI) of the left descending artery (LAD) is an extremely rare complication. We describe a case report where a patient underwent PCI of proximal LAD, complicated by loss of first septal perforator, septal infarction, and bifasicular block, which progressed to symptomatic delayed CHB. One week later, the patient required implantation of a permanent pacemaker following failure to wean off the transvenous temporary pacing maker.     

Critical review on the chemical reduction of nitroaniline

Conversion of nitroaniline (NA), a highly toxic pollutant that has been released into aquatic systems due to unmanaged industrial development in recent years, into the less harmful or a useful counterpart is the need of the hour. Various methods for its conversion and removal have been explored. Owing to its nominal features of advanced effectiveness, the chemical reduction of 4-NA using various different nanocatalytic systems is one such approach that has attracted tremendous interest over the past few years. The academic literature has been confined to case studies involving silver (Ag) and gold (Au) nanoparticles, as these are the two most widely used materials for the synthesis of nanocatalytic assemblies. Focus has also been given to sodium borohydride (NaBH₄), which is used as a reductant during the chemical reduction of NA. This systematic review summarizes the fundamentals associated with the catalytic degradation of 4-NA, and presents a comprehensive and critical study of the latest modifications used in the synthesis of these catalytic systems. In addition, the kinetics, mechanisms, thermodynamics, as well as the future directions required for understanding this model reaction, have been provided in this particular study.

Schematic illustration of catalytic reduction of 4-NA in the presence of nanocatalysts and a reducing agent.     

Identification and bioactivity evaluation of secondary metabolites from Antarctic-derived Penicillium chrysogenum CCTCC M 2020019

Extracts from Antarctic-derived Penicillium chrysogenum CCTCC M 2020019 showed potent antibacterial bioactivities. We report herein the isolation of chrysonin (1), a new compound containing a pair of enantiomers 6S- and 6R-chrysonin (1a and 1b) featuring an unprecedented eight-membered heterocycle fused with a benzene ring. Compound 2, a mixture consisting of a new zwitterionic compound chrysomamide (2a) and N-[2-trans-(4-hydroxyphenyl) ethenyl] formamide (2b) in a ratio around 1 : 2.8, was isolated together with seven known compounds 3–9. Chemical structures of all compounds were determined by comprehensive spectroscopic analyses. The isolated compounds were evaluated for antimicrobial, cytotoxic and alpha-glucosidase inhibition activities. Chrysonin (1) showed moderate alpha-glucosidase inhibitory activity. The dominant product xanthocillin X (4) displayed potent inhibition activities against Gram-negative pathogens Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa with MIC values at 0.125 μg mL⁻¹. Xanthocillins X (4) and Y1 (5) also showed significant cytotoxicities against four cancer cell lines with IC₅₀ values ranging from 0.26 to 5.04 μM. This study highlights that microorganisms from polar regions are emerging as a new resource for the discovery of natural products combating human pathogens.

The unprecedented eight-membered heterocyclic chrysonin (1) was isolated from an Antarctic fungus that also produced xanthocillins 4 and 5 as potent inhibitors against Gram-negative pathogens.     

Promising performance of chemically exfoliated Zr-doped MoS2 nanosheets for catalytic and antibacterial applications

Nanostructured materials incorporated with biological reducing agents have shown significant potential for use in bactericidal applications. Such materials have also demonstrated considerable efficacy to counter effects of chemical toxicity. In this study, nanostructured molybdenum disulfide (MoS₂) was doped with various concentrations (2.5, 5, 7.5, 10 wt%) of zirconium (Zr) using a hydrothermal route in order to assess its antimicrobial and catalytic potential. Doped and control samples were characterized with various techniques. X-ray diffraction (XRD) analysis confirmed the presence of the hexagonal phase of MoS₂ and identification of various functional groups and characteristic peaks (Mo bonding) was carried out using FTIR spectra. Micrographs obtained from FESEM and HR-TEM showed a sheet-like surface morphology, while agglomeration of nanosheets was observed upon doping with nanoparticles. To seek further clarity regarding the layered features of S–Mo–S planes, the defect densities and electronic band structure of pure MoS₂ and doped MoS₂ samples were investigated through Raman analysis. Optical properties of Zr-doped MoS₂ nanosheets were assessed using a UV-vis spectrophotometer and the results indicated a red-shift, i.e., movement of peaks towards longer wavelengths, of the material. Dynamics of migration and recombination of excited electron–hole pairs were investigated using PL spectroscopy, which was also used to confirm the presence of exfoliated nanosheets. In addition, the synthetic dye degradation potential of pure and doped samples was investigated in the presence of a reducing agent (NaBH₄). It was noted that doped MoS₂ showed superior catalytic activity compared to undoped MoS₂. The nanocatalyst synthesized in this study exhibited enhanced antibacterial activity against E. coli and S. aureus at high concentrations (0.5, 1.0 mg/50 μl). The present study suggests a cost-effective and environmentally friendly material that can be used to remove toxins such as synthetic dyes and tannery pollutants from industrial wastewater.

Nanostructured materials incorporated with biological reducing agents have shown significant potential for use in bactericidal applications.