Phosphorous and Nitrogen Dual-Doped Carbon as a Highly Efficient Electrocatalyst for Sodium-Oxygen Batteries.

Sodium-oxygen batteries have been regarded as promising energy storage devices due to their low overpotential and high energy density. Its applications, however, still face formidable challenges due to the lack of understanding about the influence of electrocatalysts on the discharge products. Here, a phosphorous and nitrogen dual-doped carbon (PNDC) based cathode is synthesized to increase the electrocatalytic activity and to stabilize the NaO superoxide nanoparticle discharge products, leading to enhanced cycling stability when compared to the nitrogen-doped carbon (NDC).

Evaluation of programmed cell death ligand 1 expression in a contemporary cohort of penile squamous cell carcinoma and its correlation with clinicopathologic and survival parameters: A study of 134 patients.

Objectives: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC.

Multifaceted Spindle Cell/Sclerosing Rhabdomyosarcoma With Role of Immunohistochemistry in Avoiding Misdiagnosis: A Multi-Institutional Study of 45 Distinct Tumors.

Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified.

Graphene Bridge for Photocatalytic Hydrogen Evolution with Gold Nanocluster Co-Catalysts.

Herein, the UV light photocatalytic activity of an AuNC-AlSrTiO-rGO nanocomposite comprising 1 wt% rGO, 0.05 wt% Au(PPh)Cl (AuNC), and AlSrTiO evaluated for H production. The synthesis of AuNC-AlSrTiO-rGO nanocomposite followed two distinct routes: (1) AuNC was first mixed with AlSrTiO followed by the addition of rGO (AuNC-AlSrTiO:rGO) and (2) AuNC was first mixed with rGO followed by the addition of AlSrTiO (AuNC-rGO:AlSrTiO).

p53 and p16 As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma.

Background: Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16 positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway.

Au-rGO nanocomposite: immobilization of phosphine-protected gold nanoclusters on reduced graphene oxide without aggregation.

Graphene supported transition metal clusters are of great interest for potential applications, such as catalysis, due to their unique properties. In this work, a simple approach to deposit Au(PPh)Cl (AuNC) on reduced graphene oxide (rGO) an method is presented. Reduction of graphene oxide at native pH (pH ≈ 2) to rGO was performed under aqueous hydrothermal conditions.

Primary round cell sarcomas of the urinary bladder with EWSR1 rearrangement: a multi-institutional study of thirteen cases with a review of the literature.

Primary Ewing sarcoma (ES) of the urinary bladder is a rare and aggressive small blue round cell malignant neoplasm associated primarily with translocation involving EWSR1 and FLI1 genes located in the 22nd and 11th chromosomes, respectively. To date, 18 cases have been published in the literature as single-case reports, based chiefly on CD99 positivity (17 patients). Molecular confirmation by fluorescence in situ hybridization was performed in 9 patients, and FLI1 immunohistochemical (IHC) analysis was not performed in any of these published cases.

Local Structure and Spectroscopic Properties of Eu-Doped BaZrO.

Pristine and Eu-doped BaZrO were synthesized via a solid-state reaction method, and the synthesized samples were systematically characterized. X-ray diffraction confirmed the formation of single and pure phases of cubic-structured BaZrO. Extended X-ray absorption fine structure (EXAFS) spectroscopy revealed the site occupancy of Eu and coordination environment around the different atomic sites.

Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches.

The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development.

High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells.

A major step toward an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env) mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers.

Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers.

Unlabelled: Due to high viral diversity, an effective HIV-1 vaccine will likely require Envs derived from multiple subtypes to generate broadly neutralizing antibodies (bNAbs). Soluble Env mimics, like the native flexibly linked (NFL) and SOSIP trimers, derived from the subtype A BG505 Env, form homogeneous, stable native-like trimers. However, other Env sequences, such as JRFL and 16055 from subtypes B and C, do so to a lesser degree.

Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design.

Viral glycoproteins mediate entry by pH-activated or receptor-engaged activation and exist in metastable pre-fusogenic states that may be stabilized by directed rational design. As recently reported, the conformationally fixed HIV-1 envelope glycoprotein (Env) trimers in the pre-fusion state (SOSIP) display molecular homogeneity and structural integrity at relatively high levels of resolution. However, the SOSIPs necessitate full Env precursor cleavage, which requires endogenous furin overexpression.

Robust neutralizing antibodies elicited by HIV-1 JRFL envelope glycoprotein trimers in nonhuman primates.

Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neutralizing monoclonal antibodies (bNabs) isolated from HIV-infected individuals efficiently recognize fully cleaved JRFL Env spikes; however, nonneutralizing gp120-directed monoclonal antibodies isolated from infected or vaccinated subjects recognize only uncleaved JRFL spikes. Therefore, as an immunogen, cleaved spikes that selectively present desired neutralizing epitopes to B cells may elicit cross-reactive neutralizing antibodies.

Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.

Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities.

Benzothiophene carboxamide derivatives as inhibitors of Plasmodium falciparum enoyl-ACP reductase.

Benzothiophene derivatives like benzothiophene sulphonamides, biphenyls, or carboxyls have been synthesized and have found wide pharmacological usage. Here we report, bromo-benzothiophene carboxamide derivatives as potent, slow tight binding inhibitors of Plasmodium enoyl-acyl carrier protein (ACP) reductase (PfENR). 3-Bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide (compound 6) is the most potent inhibitor with an IC50 of 115 nM for purified PfENR.

Beta-ketoacyl-ACP synthase I/II from Plasmodium falciparum (PfFabB/F)--is it B or F?

Condensing enzymes play an important and decisive role in terms of fatty acid composition of any organism. They can be classified as condensing enzymes involved in initiating the cycle and enzymes involved in elongating the initiated fatty acyl chain. In E.

Combined effect of epigallocatechin gallate and triclosan on enoyl-ACP reductase of Mycobacterium tuberculosis.

Among the various inhibitors known for enoyl-acyl carrier protein (ACP) reductases, triclosan and green tea catechins are two promising candidates. In the present study, we show, for the first time that epigallocatechin gallate (EGCG), a major component of green tea catechins, inhibits InhA, the enoyl-ACP reductase of Mycobacterium tuberculosis with an IC50 of 17.4muM.

Self-acylation properties of type II fatty acid biosynthesis acyl carrier protein.

Acyl carrier protein (ACP) plays a central role in many metabolic processes inside the cell, and almost 4% of the total enzymes inside the cell require it as a cofactor. Here, we report self-acylation properties in ACPs from Plasmodium falciparum and Brassica napus that are essential components of type II fatty acid biosynthesis (FAS II), disproving the existing notion that this phenomenon is restricted only to ACPs involved in polyketide biosynthesis. We also provide strong evidence to suggest that catalytic self-acylation is intrinsic to the individual ACP.

Mass spectrometry-based systems approach for identification of inhibitors of Plasmodium falciparum fatty acid synthase.

The emergence of strains of Plasmodium falciparum resistant to the commonly used antimalarials warrants the development of new antimalarial agents. The discovery of type II fatty acid synthase (FAS) in Plasmodium distinct from the FAS in its human host (type I FAS) opened up new avenues for the development of novel antimalarials. The process of fatty acid synthesis takes place by iterative elongation of butyryl-acyl carrier protein (butyryl-ACP) by two carbon units, with the successive action of four enzymes constituting the elongation module of FAS until the desired acyl length is obtained.

Discovery of a rhodanine class of compounds as inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase.

Enoyl acyl carrier protein (ACP) reductase, one of the enzymes of the type II fatty acid biosynthesis pathway, has been established as a promising target for the development of new drugs for malaria. Here we present the discovery of a rhodanine (2-thioxothiazolidin-4-one) class of compounds as inhibitors of this enzyme using a combined approach of rational selection of compounds for screening, analogue search, docking studies, and lead optimization. The most potent inhibitor exhibits an IC(50) of 35.

Packing and loop-structure variations in non-isomorphous crystals of FabZ from Plasmodium falciparum.

The crystals obtained from various batches of crystallization trials of FabZ from Plasmodium falciparum exhibited non-isomorphism. The c axis of the I222 cell showed a large variation of about 16 A, from c = 81 A to c = 97 A. Complete data sets were collected for three crystal forms with varying lengths of the c axis (form 1, c = 97 A; form 2, c = 92 A; form 3, c = 81 A).