Solid-State NMR Study to Probe the Effects of Divalent Metal Ions (Ca2+ and Mg2+) on the Magnetic Alignment of Polymer-Based Lipid Nanodiscs.

Divalent cations, especially Ca2+ and Mg2+, play a vital role in the function of biomolecules and making them important to be constituents in samples for in vitro biophysical and biochemical characterizations. Although lipid nanodiscs are becoming valuable tools for structural biology studies on membrane proteins and for drug delivery, most types of nanodiscs used in these studies are unstable in the presence of divalent metal ions. To avoid the interaction of divalent metal ions with the belt of the nanodiscs, synthetic polymers have been designed and demonstrated to form stable lipid nanodiscs under such unstable conditions. Such polymer-based nanodiscs have been shown to provide an ideal platform for structural studies using both solid-state and solution NMR spectroscopies because of the near-native cell-membrane environment they provide and the unique magnetic-alignment behavior of large-size nanodiscs. In this study, we report an investigation probing the effects of Ca2+ and Mg2+ ions on the formation of polymer-based lipid nanodiscs and the magnetic-alignment properties using a synthetic polymer, styrene maleimide quaternary ammonium (SMA-QA), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids. Phosphorus-31 NMR experiments were used to evaluate the stability of the magnetic-alignment behavior of the nanodiscs for varying concentrations of Ca2+ or Mg2+ at different temperatures. It is remarkable that the interaction of divalent cations with lipid headgroups promotes the stacking up of nanodiscs that results in the enhanced magnetic alignment of nanodiscs. Interestingly, the reported results show that both the temperature and the concentration of divalent metal ions can be optimized to achieve the optimal alignment of nanodiscs in the presence of an applied magnetic field. We expect the reported results to be useful in the design of nanodisc-based nanoparticles for various applications in addition to atomic-resolution structural and dynamics studies using NMR and other biophysical techniques.

Nanomaterials for oncotherapies targeting the hallmarks of cancer.

An increasing amount of evidence has demonstrated the diverse functionalities of nanomaterials in oncotherapies such as drug delivery, imaging, and killing cancer cells. This review aims to offer an authoritative guide for the development of nanomaterial-based oncotherapies and shed light on emerging yet understudied hallmarks of cancer where nanoparticles can help improve cancer control. With this aim, three nanomaterials, i.e. those based on gold, graphene, and liposome, were selected to represent and encompass metal inorganic, nonmetal inorganic, and organic nanomaterials, and four oncotherapies, i.e. phototherapies, immunotherapies, cancer stem cell therapies, and metabolic therapies, were characterized based on the differential hallmarks of cancer that they target. We also view physical plasma as a cocktail of reactive species and carrier of nanomaterials and focus on its roles in targeting the hallmarks of cancer provided with its unique traits and ability to selectively induce epigenetic and genetic modulations in cancer cells that halt tumor initiation and progression. This review provides a clear understanding of how the physico-chemical features of particles at the nanoscale contribute alone or create synergistic effects with current treatment modalities in combating each of the hallmarks of cancer that ultimately leads to desired therapeutic outcomes and shapes the toolbox for cancer control.

Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry.

Rational: The mutating SARS-CoV-2 potentially impairs the efficacy of current vaccines or antibody-based treatments. Broad-spectrum and rapid anti-virus methods feasible for regular epidemic prevention against COVID-19 or alike are urgently called for. Methods: Using SARS-CoV-2 virus and bioengineered pseudoviruses carrying ACE2-binding spike protein domains, we examined the efficacy of cold atmospheric plasma (CAP) on virus entry prevention. Results: We found that CAP could effectively inhibit the entry of virus into cells. Direct CAP or CAP-activated medium (PAM) triggered rapid internalization and nuclear translocation of the virus receptor, ACE2, which began to return after 5 hours and was fully recovered by 12 hours. This was seen in vitro with both VERO-E6 cells and human mammary epithelial MCF10A cells, and in vivo. Hydroxyl radical (·OH) and species derived from its interactions with other species were found to be the most effective CAP components for triggering ACE2 nucleus translocation. The ERα/STAT3(Tyr705) and EGFR(Tyr1068/1086)/STAT3(Tyr705) axes were found to interact and collectively mediate the effects on ACE2 localization and expression. Conclusions: Our data support the use of PAM in helping control SARS-CoV-2 if developed into products for nose/mouth spray; an approach extendable to other viruses utilizing ACE2 for host entry.

Cantharidin-loaded biomimetic MOF nanoparticle cascade to enhance the Fenton reaction based on amplified photothermal therapy.

The treatment efficiency of the Fenton reaction is expected to be greatly restricted due to problems such as inefficient delivery of Fenton catalysis, limited H2O2 concentration and uneven tumour tissue. Accurate photothermal therapy (PTT) could improve the efficiency of Fenton catalysis to some extent by raising the temperature. However, the heat shock response (HSR) of tumour cells caused by PTT and Fenton reaction would attenuate the treatment effect. In this study, we developed an iron ions-mediated Fenton reaction combined with a PTT treatment platform based on a metal-organic framework, i.e., PPy-CTD@MIL-100@MPCM nanoparticles (PCMM NPs), and further explored the inhibitory effect of PCMM NPs on the heat shock response (HSR). PCMM NPs could accumulate in tumour tissue via the coated macrophage cell membranes (MPCMs) to target inflammatory tissues. The photothermal effect of polypyrrole (PPy) accelerated the release of cantharidin (CTD) and iron ions loaded in the PCMM NPs. CTD, as an HSR inhibitor, could inhibit this response of tumour cells and improve the effect of PTT. Meanwhile, the heat generated during the PTT process could improve the efficiency of the Fenton reaction. This study suggested that PCMM NPs could serve as a combined treatment platform to enhance the Fenton reaction based on amplified photothermal therapy.

CytoMegaloVirus Infection Database: A Public Omics Database for Systematic and Comparable Information of CMV.

CytoMegaloVirus (CMV) is known to cause infection in humans and may remain dormant throughout the life span of an individual. CMV infection has been reported to be fatal in patients with weak immunity. It is transmitted through blood, saliva, urine, semen and breast milk. Although medications are available to treat the infected patients, there is no cure for CMV. This concern prompted us to construct a comprehensive database having exhaustive information regarding CMV, its infections and therapies to be available on a single platform. Thus, we propose a newly designed database that includes all the information from various public resources such as biological databases, virus taxonomy databanks, viral databases, and drug bank, integrated into this database, named as cytomegalovirus database (CMVdb). It features all the relevant data regarding the strains of CMV, genes, expressed proteins, the genomic sequence of CMV and drugs used in the treatment of cytomegalovirus infection. CMVdb has a unique feature of in-house data analysis, so all the data obtained from various resources are processed within the system. The user interface is more responsive because of the integrated platform that will highly facilitate the researchers. Based on CMVdb functionality and quality of the data, it will accelerate the research and development in the field of infectious diseases and immunology with a special focus on CMV. The obtained data would be useful in designing better therapeutic strategies and agents for the treatment of CMV infections. The proposed database (CMVdb) is freely accessible at http://shaktisahislab.com/include/CMV/ or http://weislab.com/WeiDOCK/include/content/CMV/.

Implants placed simultaneously with maxillary sinus floor augmentation in the presence of antral pseudocysts: Presentation of a case series.

OBJECTIVE: To report the outcome of simultaneous placement of dental implants with maxillary sinus elevation in the presence of antral pseudocysts. METHOD AND MATERIALS: This case series involved 14 patients with 28 implants placed simultaneously with maxillary sinus elevation. The psuedocysts were treated by cystic fluid extraction. Postoperative examinations were performed at 3, 6, and 12 months. RESULTS: All restorations were finished 6 to 9 months after implant placement. Nine antral pseudocysts disappeared and five decreased in size. All implants were deemed successful at 1 year postoperatively, showing osseointegration and masticatory function. No mobility was found during the follow-up period. CONCLUSION: In the absence of maxillary sinus infection, the combination of cystic fluid extraction, maxillary sinus elevation, and immediate implantation showed an acceptable clinical outcome in this series of patients.

[Clinical study of simultaneous implantation in maxillary molar area after bone graft in patients with residual alveolar bone height<3 mm].

PURPOSE: To evaluate the clinical effect of maxillary sinus floor elevation and simultaneous implant in patients with residual alveolar bone height <3 mm in the posterior maxillary sinus area. METHODS: From April 1, 2012 to December 31, 2015, 56 patients with lost maxillary posterior teeth and residual alveolar bone height <3 mm were enrolled in this study. During operation, maxillary sinus floor elevation was performed and implants were placed simultaneously. Patients were followed up for 3, 6 and 12 months (range: 6-12 months) to analyze and evaluate the postoperative healing effect. RESULTS: A total of 52 implants were placed in 38 patients. During the follow-up period, all patients had good osterintegration of the implants and the surrounding bony tissues. Efficient mastication was obtained. The color and shape of gingiva returned to normal. No complications occurred. The surgical success rate was 100%. CONCLUSIONS: For patients with residual alveolar bone height <3 mm, maxillary sinus floor elevation and simultaneous implant in patients can also obtain good therapeutic effect.