Computational design of transmembrane pores.

Transmembrane channels and pores have key roles in fundamental biological processes1 and in biotechnological applications such as DNA nanopore sequencing2-4, resulting in considerable interest in the design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels5,6, and there have been recent advances in de novo membrane protein design7,8 and in redesigning naturally occurring channel-containing proteins9,10. However, the de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores remains an outstanding challenge11,12. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments show that, when expressed in insect cells, the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modification at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications.

Unique Reaction-Based Polynorbornene Sensing Probes for Ultrasensitive Detection of Hydrazine in Both Environmental and Biological Systems.

Hydrazine-mediated formation of 1,4-phthalazinedione analogues from phthalimide-like components has been utilized to formulate fluorescent probe NorTh. A turn-on fluorescent process has been evaluated to detect hydrazine in a highly selective manner by a small molecular probe NorTh and its homopolymer Poly-NorTh. Both these probes have been evaluated as excellent candidates for nanomolar level detection of hydrazine with a time frame of <15 min, which is rapid in terms of real application. Due to the reaction-based detection process, we have achieved high selectivity for our probes toward the identification of hydrazine in the presence of metal ions, anions, amino acids, and various amines. Limit of detection values are 16 and 35 nM for NorTh and Poly-NorTh, respectively, which are well below the permissible limit given by WHO and EPA. Poly-NorTh has been utilized to detect hydrazine in environmental water samples, soil samples, and biological samples to establish the applicability of our probes in real-field scenarios. We introduce an easy-to-synthesize, cheap, and small molecular probe and its polymer for ultrafast, highly selective, and sensitive detection of hydrazine in all possible mediums to counter the hydrazine toxicity through fluorescence turn-on signal output.

Molecular insights on Eltrombopag: potential mitogen stimulants, angiogenesis, and therapeutic radioprotectant through TPO-R activation.

The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed to evaluate the stability of the ligand across specific proteins, showing favorable characteristics. For the first time, we examined the presence of TPO-R in human umbilical cord mesenchymal stem cells (hUCMSC) and human gingival mesenchymal stem cells (hGMSC) proliferation. Furthermore, treatment with EPAG demonstrated angiogenesis and vasculature formation of endothelial lineage derived from both MSCs. It also indicated the activation of critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, and FLI-1. Additional experiments confirmed that EPAG could be an ideal molecule for protecting against UVB radiation damage, as gene expression (JAK-2, ERK-2, MCL-1, NFkB, and STAT-3) and protein CD90/cMPL analysis showed TPO-R activation in both hUCMSC and hGMSC. Overall, EPAG exhibits significant potential in treating radiation damage and mitigating the side effects of radiotherapy, warranting further clinical exploration.

What is the context?● Chemotherapy, radiation treatment, or immunological disorders can cause a decrease in platelet count (thrombocytopenia) or decrease all blood cell types (pancytopenia) in the bone marrow. This can make it challenging to choose the appropriate cancer treatment plan.● Eltrombopag (EPAG) is an oral non-peptide thrombopoietin (TPO) mimetic that activates the cMPL receptor in the body. This activation leads to cell differentiation and proliferation, stimulating platelet production and reducing thrombocytopenia. The cMPL receptor is present in liver cells, megakaryocytes, and hematopoietic cells. However, its effects on stem cell proliferation and differentiation are not entirely understood.What is the new?● This study delves into the molecular interactions and therapeutic applications of EPAG, a small molecule that activates cMPL (TPO-R).● The study offers a comprehensive analysis of the ligand-receptor complex formation, including an examination of downstream signaling elements. Furthermore, molecular dynamics simulations demonstrate the stability of the ligand when interacting with targeted proteins.● The research investigates the presence of TPO-R on stem cell-derived endothelial cells, shedding insight into the ability of EPAG TPO-mimetic to promote angiogenesis and vasculature formation.● The study revealed that EPAG has the potential to protect against UVB-induced radiation damage and stimulate stem cell growth.What is the implications?The study emphasizes the potential of EPAG as a promising option for addressing radiation injury and minimizing the adverse effects of radiotherapy. It could revolutionize treatments not only for thrombocytopenia but also for enhancing the growth of stem cells. Furthermore, the research deepens our understanding of EPAG's molecular mechanisms, providing valuable insights for developing future drugs and therapeutic approaches for cell therapy to treat radiation damage.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis.

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Sticking Together: Injectable Granular Hydrogels with Increased Functionality via Dynamic Covalent Inter-Particle Crosslinking.

Granular hydrogels are an exciting class of microporous and injectable biomaterials that are being explored for many biomedical applications, including regenerative medicine, 3D printing, and drug delivery. Granular hydrogels often possess low mechanical moduli and lack structural integrity due to weak physical interactions between microgels. This has been addressed through covalent inter-particle crosslinking; however, covalent crosslinking often occurs through temporal enzymatic methods or photoinitiated reactions, which may limit injectability and material processing. To address this, a hyaluronic acid (HA) granular hydrogel is developed with dynamic covalent (hydrazone) inter-particle crosslinks. Extrusion fragmentation is used to fabricate microgels from photocrosslinkable norbornene-modified HA, additionally modified with either aldehyde or hydrazide groups. Aldehyde and hydrazide-containing microgels are mixed and jammed to form adhesive granular hydrogels. These granular hydrogels possess enhanced mechanical integrity and shape stability over controls due to the covalent inter-particle bonds, while maintaining injectability due to the dynamic hydrazone bonds. The adhesive granular hydrogels are applied to 3D printing, which allows the printing of structures that are stable without any further post-processing. Additionally, the authors demonstrate that adhesive granular hydrogels allow for cell invasion in vitro. Overall, this work demonstrates the use of dynamic covalent inter-particle crosslinking to enhance injectable granular hydrogels.

Elaboration, Characterization and Thermal Decomposition Kinetics of New Nanoenergetic Composite Based on Hydrazine 3-Nitro-1,2,4-triazol-5-one and Nanostructured Cellulose Nitrate.

This research aims to develop new high-energy dense ordinary- and nano-energetic composites based on hydrazine 3-nitro-1,2,4-triazol-5-one (HNTO) and nitrated cellulose and nanostructured nitrocellulose (NC and NMCC). The elaborated energetic formulations (HNTO/NC and HNTO/NMCC) were fully characterized in terms of their chemical compatibility, morphology, thermal stability, and energetic performance. The experimental findings implied that the designed HNTO/NC and HNTO/NMCC formulations have good compatibilities with attractive characteristics such as density greater than 1.780 g/cm3 and impact sensitivity around 6 J. Furthermore, theoretical performance calculations (EXPLO5 V6.04) displayed that the optimal composition of the as-prepared energetic composites yielded excellent specific impulses and detonation velocities, which increased from 205.7 s and 7908 m/s for HNTO/NC to 209.6 s and 8064 m/s for HNTO/NMCC. Moreover, deep insight on the multi-step kinetic behaviors of the as-prepared formulations was provided based on the measured DSC data combined with isoconversional kinetic methods. It is revealed that both energetic composites undergo three consecutive exothermic events with satisfactory activation energies in the range of 139-166 kJ/mol for HNTO/NC and 119-134 kJ/mol for HNTO/NMCC. Overall, this research displayed that the new developed nanoenergetic composite based on nitrated cellulose nanostructure could serve as a promising candidate for practical applications in solid rocket propellants and composite explosives.

Effectiveness and safety of tacrolimus with or without eltrombopag, as a part of immunosuppressive treatment of aplastic anemia in adults: a retrospective case series.

First-line treatment of aplastic anemia(AA) and for AA patients ineligible for hematopoietic stem cell transplantation (HSCT) has consisted of antithymocyte globulin (ATG), the calcineurin inhibitor cyclosporine A (CsA), and more recently eltrombopag. However, at our institution, we have successfully substituted another calcineurin inhibitor, tacrolimus, as a part of immunosuppressive threatment (IST) for AA due to more favorable toxicity profile. Since there is limited data on the use of tacrolimus in aplastic anemia, we conducted a retrospective review of twenty patients treated with tacrolimus-based immunosuppressive therapy (IST) as a first- or second-line treatment. The overall response rate was comparable to that of patients treated with CsA (18 patients). However, there were no cutaneous side effects observed in patients receiving tacrolimus, a relatively common finding with CsA use. Our data suggest that tacrolimus-based IST is a potential option in AA and might have a more favorable toxicity profile compared to CsA.

Hydrazine-Enabled One-Step Synthesis of Metal Nanoparticle-Functionalized Gradient Porous Poly(ionic liquid) Membranes.

In this communication, a one-step synthetic route is reported toward free-standing metal-nanoparticle-functionalized gradient porous polyelectrolyte membranes (PPMs). The membranes are produced by soaking a glass-plate-supported blend film that consists of a hydrophobic poly(ionic liquid) (PIL), poly(acrylic acid), and a metal salt, into an aqueous hydrazine solution. Upon diffusion of water and hydrazine molecules into the blend film, a phase separation process of the hydrophobic PIL and an ionic crosslinking reaction via interpolyelectrolyte complexation occur side by side to form the PPM. Simultaneously, due to the reductive nature of hydrazine, the metal salt inside the polymer blend film is reduced in situ by hydrazine into metal nanoparticles that anchor onto the PPM. The as-obtained hybrid porous membrane is proven functional in the catalytic reduction of p-nitrophenol. This one-step method to grow metal nanoparticles and gradient porous membranes can simplify future fabrication processes of multifunctional PPMs.

Observing Malondialdehyde-Mediated Signaling Pathway in Cerebral Ischemia Reperfusion Injury with a Specific Nanolight.

Cerebral ischemia reperfusion injury (CIRI) is closely related to lipid peroxidation. Malondialdehyde (MDA), as a biomarker of lipid peroxidation, is prone to addition with biomacromolecules, resulting in a secondary cerebral injury. However, desirable tools for in vivo-determining cerebral MDA are scarce. Thus, we devised innovative polymer carbon dots carbonized by benzoyl hydrazine and named them BH-PCDs. BH-PCDs covered with hydrazine groups directly form from one-pot synthesis. The functional nanoparticle specifically identifies MDA via a photoinduced electron transfer (PET) mechanism from other similar biological species, especially reactive carbonyl species. BH-PCDs afforded several valuable traits of a simple preparation, a large two-photon absorption cross section, and exceptional biocompatibility, as well as the ability of traversing the blood-brain barrier. Relying on BH-PCDs, we real-time portrayed the increased cerebral MDA under CIRI. Furthermore, combining with a commercial indicator of the superoxide anion (O2•-), an O2•--regulated MDA level under CIRI was visualized in vivo. Moreover, we demonstrated MDA inactivated glutamine synthetase under CIRI, mediating the glutamate level. Overall, we provide a perspective nanolight serviceable for treating CIRI, which could reveal the physiopathology mechanism of brain MDA.

Real time detection and monitoring of 2, 4-dinitrophenylhydrazine in industrial effluents and water bodies by electrochemical approach based on novel conductive polymeric composite.

Much attention has been given to detection and monitoring of hydrazine-based compounds in recent time because of its significant negative impacts on human health and ecosystem (aquatic lives). This prompted the current study focusing on detection of 2, 4-dinitrophenylhydrazine (2, 4-dnphz) using electrochemically synthesized poly-para amino benzoic acid-manganese oxide (P-pABA-MnO2) composite film. The synthesized P-pABA-MnO2 composite film was characterized in terms of its structural and morphological properties by X-ray diffraction spectroscopy and field emission scanning electron microscopy respectively. In addition, functionalities and binding energy of p-PABA-MnO2 were confirmed using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy respectively. Finally, electrochemical properties were investigated using electrochemical impedance spectroscopy and cyclic voltammetry. The synthesized P-pABA-MnO2 displayed good electrocatalytic reduction property towards 2, 4-dnphz with ultra-low limit of detection (0.08 µM; S/N = 3) and very high sensitivity (52 µAµ-1Mcm-2). The proposed sensor based on P-pABA-MnO2 also demonstrated good stability in terms of repeatability, reproducibility and interferents effects. Lastly, the proposed sensor was satisfactorily used in detection of 2, 4-dnphz in environmental real samples.

Gold nanorod-loaded (PLGA-PEG) nanocapsules as near-infrared controlled release model of anticancer therapeutics.

Despite of high in vitro anticancer efficacy of many chemotherapeutics, their in vivo use is limited due to lack of biocompatibility and tumor targeting. Near-infrared (NIR) photothermally induced phase transition of PLGA-PEG regime was utilized for developing highly efficient photoresponsive drug delivery systems. Co-encapsulation of plasmonic gold nanorods (GNRs), as NIR-trigger, with the novel and highly efficient anticancer drug N'-(2-Methoxybenzylidene)-3-methyl-1-phenyl-H-Thieno[2,3-c]Pyrazole-5-Carbohyd-razide (MTPC) produced NIR-responsive biodegradable polymeric (PLGA-b-PEG) nanocapsules. This remotely controllable drug release significantly enhanced both biodistribution and pharmacokinetics of the hydrophobic drug. Intravenous (IV) injection of the prepared nanocapsules (MTPC/GNRs@PLGA-PEG) to tumor-bearing mice followed by extracorporeal exposure of the tumor to NIR light resulted in highly selective drug accumulation at the tumor sites. In vivo biodistribution and pharmacokinetics utilizing iodine-131 drug-radiolabelling technique revealed a maximum target to non-target ratio (T/NT) of 5.8, 4 h post-injection with maximum drug level in the tumor (6.3 ± 0.6% of the injected dose). Graphical abstract.

Development and optimization of levodopa and benzylhydrazine orally disintegrating tablets by direct compression and response surface methodology.

The number of Parkinson's disease (PD) patients with the advanced phase and motor fluctuations is increasing. The objective of this study is developing levodopa/benzylhydrazine orally disintegrating tablets (L/B ODTs), which would provide greater convenience and ease of use than conventional tablets for these patients. In the present study, the L/B ODTs were developed successfully with an optimized formulation using response surface methodology (RSM). The direct compression technology was employed for the preparation of L/B ODTs. Considerably shorter disintegration time and faster dissolution profile were obtained under the optimum formulation with microcrystalline cellulose 25.7%, cross-polyvinylpyrrolidone 6.22% and Sodium carboxymethyl starch 5.36%. The content uniformity (%) of levodopa and benzylhydrazine was 50 ± 1.4% and 14.25 ± 0.6%, respectively. Thickness, friability, hardness and wetting time were 2.8 ± 0.05 mm, 0.46 ± 0.21%, 5.42 ± 1.1 kp and 31.2 ± 2.1 s, respectively, and all of data well comply with the General Principles of the Chinese Pharmacopeia. Mannitol of 22% in formulation could bring a pleasant taste: sweet, cool and refreshing. Almost all the volunteers felt that the ODTs had good taste, no roughness, and no gritty feeling, indicating that the ODTs prepared had good palatability, so patients will have good compliance when taking medicine.

Supramolecular Interactions in Hybrid Polylactide Blends-The Structures, Mechanisms and Properties.

The conformation of polylactide (PLA) chains can be adjusted by supramolecular interactions (the formation of hydrogen bonds or host-guest complexes) with appropriate organic molecules. The structures formed due to those intermolecular interactions may act as crystal nuclei in the PLA matrix ("soft templating"). In this review, the properties of several supramolecular nucleating systems based on synthetic organic nucleators (arylamides, hydrazides, and 1,3:2,4-dibenzylidene-d-sorbitol) are compared to those achieved with biobased nucleating agents (orotic acid, humic acids, fulvic acids, nanocellulose, and cyclodextrins) that can also improve the mechanical properties of PLA. The PLA nanocomposites containing both types of nucleating agents/additives are discussed and evaluated in the context of their biomedical applicability.

Cellulose Acetate Fabrics Loaded with Rhodamine B Hydrazide for Optical Detection of Cu(II).

In this work, different materials were fabricated from cellulose acetate, loaded with rhodamine B hydrazide and tested as Cu(II) optical sensor. We prepared membranes displaying a sub-micron porous structure using the phase inversion technique, clusters of fibers with varying diameter depending on the preparation procedure using electrospinning, and casted films presenting a smooth non porous structure. Loading of rhodamine B hydrazide on the fabrics after their production was found to be the best procedure to ensure the stability of the dye in the polymeric materials. Absorption and emission analysis of the solid substrates revealed the presence of the dye on the porous fabrics and allowed to choose the most suited materials and loading conditions to test their response towards Cu(II) ions. Reaction of the loaded rhodamine B hydrazide with Cu(II) was confirmed by absorption and emission spectroscopies and by confocal fluorescence imaging, through detection of the product rhodamine B. The results point to promising sensing applications of the prepared composite materials.

Exploitation of nitric oxide donors to control bacterial adhesion on ready-to-eat vegetables and dispersal of pathogenic biofilm from polypropylene.

BACKGROUND: Nitric oxide (NO) donors have been used to control biofilm formation. Nitric oxide can be delivered in situ using organic carriers and acts as a signaling molecule. Cells exposed to NO shift from biofilm to the planktonic state and are better exposed to the action of disinfectants. In this study, we investigate the capability of the NO donors molsidomine, MAHAMA NONOate, NO-aspirin and diethylamine NONOate to act as anti-adhesion agents on ready-to-eat vegetables, as well as dispersants for a number of pathogenic biofilms on plastic. RESULTS: Our results showed that 10 pM molsidomine reduced the attachment of Salmonella enterica sv Typhimurium 14 028 to pea shoots and coriander leaves of about 0.5 Log(CFU/leaf) when compared with untreated control. The association of 10 pmol L-1 molsidomine with 0.006% H2 O2 showed a synergistic effect, leading to a significant reduction in cell collection on the surface of the vegetable of about 1 Log(CFU/leaf). Similar results were obtained for MAHMA NONOate. We also showed that the association of diethylamine NONOate at 10 mmol L-1 and 10 pmol L-1 with the quaternary ammonium compound diquat bromide improved the effectiveness of biofilm dispersal by 50% when compared with the donor alone. CONCLUSIONS: Our findings reveal a dual role of NO compounds in biofilm control. Molsidomine, MAHMA NONOate, and diethylamine NONOate are good candidates for either preventing biofilm formation or dispersing biofilm, especially when used in conjunction with disinfectants. Nitric oxide compounds have the potential to be developed into a toolkit for pro-active practices for good agricultural practices (GAPs), hazard analysis and critical control points (HACCP), and cleaning-in-place (CIP) protocols in industrial settings where washing is routinely applied. © 2020 Society of Chemical Industry.

Polyhydrazide-Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels.

Reported herein is a series of pore-containing polymeric nanotubes based on a hydrogen-bonded hydrazide backbone. Nanotubes of suitable lengths, possessing a hollow cavity of about a 6.5 Šdiameter, mediate highly efficient transport of diverse types of anions, rather than cations, across lipid membranes. The reported polymer channel, having an average molecular weight of 18.2 kDa and 3.6 nm in helical height, exhibits the highest anion-transport activities for iodide (EC50 =0.042 µm or 0.028 mol % relative to lipid), whcih is transported 10 times more efficiently than chlorides (EC50 =0.47 µm). Notably, even in cholesterol-rich environment, iodide transport activity remains high with an EC50 of 0.37 µm. Molecular dynamics simulation studies confirm that the channel is highly selective for anions and that such anion selectivity arises from a positive electrostatic potential of the central lumen rendered by the interior-pointing methyl groups.

A Phase II Trial of Selinexor (KPT-330) for Metastatic Triple-Negative Breast Cancer.

LESSONS LEARNED: Single-agent selinexor has limited activity in heavily pretreated patients with metastatic triple-negative breast cancer.Selinexor 60 mg by mouth twice weekly was generally well tolerated with a side-effect profile consistent with previous clinical trials.Future studies of selinexor in this population should focus on combination approaches and a biomarker-driven strategy to identify patients most likely to benefit. BACKGROUND: This phase II trial evaluated the safety, pharmacodynamics, and efficacy of selinexor (KPT-330), an oral selective inhibitor of nuclear export (SINE) in patients with advanced triple-negative breast cancer (TNBC). METHODS: This phase II trial was designed to enroll 30 patients with metastatic TNBC. Selinexor was given at 60 mg orally twice weekly on days 1 and 3 of each week, three of each 4-week cycle. The primary objective of this study was to determine the clinical benefit rate (CBR), defined as complete response + partial response + stable disease (SD) ≥12 weeks. RESULTS: Ten patients with a median age of 60 years (range 44-71 years) were enrolled between July 2015 and January 2016. The median number of prior chemotherapy lines was 2 (range 1-5). A planned interim analysis for the first stage per protocol was performed. Three patients had SD and seven had progressive disease. On the basis of these results and predefined stoppage rules, the study was halted. CONCLUSION: Selinexor was fairly well tolerated in patients with advanced TNBC but did not result in objective responses. However, clinical benefit rate was 30%, and further investigation of selinexor in this patient population should focus on combination therapies.

A Metal-Doped Fungi-Based Biomaterial for Advanced Electrocatalysis.

Nature and its highly sophisticated biomaterials are an endless source of inspiration for engineers and scientists across a wide range of disciplines. During the last decade, concepts of bioinspired synthesis of hierarchically structured nano- and micromaterials have been attracting increasing attention. In this article, we have utilized the natural ability of fungi to absorb metal ions for a bioinspired synthesis of carbonaceous material doped by selected transition metals. As an all-around metal accumulator, Hebeloma mesophaeum was selected, and it was cultivated in the presence of three transition-metal ions: NiII , FeII , and MnII . The metal-doped carbonized biomaterial possessed enhanced catalytic activity toward hydrazine oxidation, oxygen reduction, and cumene hydroperoxide reduction. Thus, we have shown possible transformation of a waste product (fungi grown on a contaminated soil) into a value-added carbonaceous material with tailored catalytic properties. This bioinspired synthesis can outline an attractive route for the fabrication of catalysts for important industrial applications on a large scale.

The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.

The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.

Efficient enrichment of glycopeptides by supramolecular nanoassemblies that use proximity-assisted covalent binding.

Mass spectrometry (MS)-based analysis of glycoproteins and glycopeptides requires selective separation strategies to eliminate interferences from more abundant non-glycosylated biomolecules. In this work, we describe a two-phase liquid-liquid extraction method using supramolecular polymeric nanoassemblies that can selectively and efficiently enrich glycopeptides for enhanced MS detection. The polymeric nanoassemblies are made selective for glycopeptides via the incorporation of hydrazide functional groups that covalently bind to glycans. The enrichment efficiency is further enhanced via the incorporation of acidic functional groups that lead to a proximity-assisted catalysis of the hydrazide-glycan conjugation reaction. Our results further demonstrate the value of designer supramolecular nanomaterials for the selective enrichment of modified peptides from complicated mixtures.