Buffalo BioLabs

Amyloid beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles (NFTs) are the histopathological hallmarks of Alzheimer's disease (AD) and targets for AD therapeutics. Since Aβ and tau pathologies both drive AD pathogenesis and progression, immunotherapies singularly targeting either Aβ or tau may be limited, and simultaneously targeting multiple epitopes of both Aβ and tau may be an efficacious approach. We developed a novel vaccine including three his-tagged tau peptides, tau1-22, mid-region tau171-191 (taupT181), and tau388-407 (taupS396/S404), as well as two his-tagged Aβ fragments (N-terminal Aβ1-14 and N-terminal pyroglutamate AβpE3-14) with the spontaneous nanoliposome antigen particle (SNAP) system, termed SNAP-AD5. Intramuscular vaccination of nine to ten months old of 3xTg-AD mice and age-matched wild-type control animals with SNAP-AD5 or adjuvant only, once every three weeks for a total of 5 immunizations, simultaneously produced IgG titers of antibody against their specific antigens, significantly decreased Aβ and tau pathologies, and effectively improved cognitive function. SNAP-AD5 was well tolerated without any detectable adverse side effects, including inflammatory responses in the peripheral circulation and in the brain, and hemorrhages in the mouse brain. These results support that SNAP-AD5 simultaneously targeting both Aβ and tau is potentially a promising new approach for treating AD. Further optimization and development of the SNAP-AD5 vaccine for treating AD is warranted.

Background: Melanoma metastasis, driven by tumor microenvironment (TME)-mediated crosstalk facilitated by extracellular vesicles (EVs), remains a major therapeutic challenge. A critical barrier to clinical translation is the overlap in protein cargo between tumor-derived and healthy cell EVs. Objective: To address this, we developed Scaffold-free Functional Deconvolution (SFD), a novel computational approach that leverages a comprehensive healthy cell EV protein database to deconvolute non-oncogenic background signals. Methods: Beginning with 1915 proteins (identified by MS/MS analysis on an Orbitrap Fusion Lumos Mass Spectrometer using the IonStar workflow) from melanoma EVs isolated using REIUS, SFD applies four sequential filters: exclusion of normal melanocyte EV proteins, prioritization of metastasis-linked entries (HCMDB), refinement via melanocyte-specific databases, and validation against TCGA survival data. Results: This workflow identified 21 high-confidence targets implicated in metabolic-associated acidification, immune modulation, and oncogenesis, and were analyzed for reduced disease-free and overall survival. SFD's versatility was further demonstrated by surfaceome profiling, confirming enrichment of H7-B3 (CD276), ICAM1, and MIC-1 (GDF-15) in metastatic melanoma EV via Western blot and flow cytometry. Meta-analysis using Vesiclepedia and STRING categorized these targets into metabolic, immune, and oncogenic drivers, revealing a dense interaction network. Conclusions: Our results highlight SFD as a powerful tool for identifying clinically relevant biomarkers and therapeutic targets within melanoma EVs, with potential applications in drug development and personalized medicine.

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized by nerve degeneration distal to the site of nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of “accepting” innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generate a mouse model in which NANOG, a pluripotency-associated transcription factor is expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulates the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression leads to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation. Further, NANOG mice demonstrate extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice show greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI.

Tumors activate protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK, also called EIF2AK3) in response to hypoxia and nutrient deprivation as a stress-mitigation strategy. Here, we tested the hypothesis that inhibiting PERK with HC-5404 enhances the antitumor efficacy of standard-of-care VEGF receptor tyrosine kinase inhibitors (VEGFR-TKI). HC-5404 was characterized as a potent and selective PERK inhibitor, with favorable in vivo properties. Multiple renal cell carcinoma (RCC) tumor models were then cotreated with both HC-5404 and VEGFR-TKI in vivo, measuring tumor volume across time and evaluating tumor response by protein analysis and IHC. VEGFR-TKI including axitinib, cabozantinib, lenvatinib, and sunitinib induce PERK activation in 786-O RCC xenografts. Cotreatment with HC-5404 inhibited PERK in tumors and significantly increased antitumor effects of VEGFR-TKI across multiple RCC models, resulting in tumor stasis or regression. Analysis of tumor sections revealed that HC-5404 enhanced the antiangiogenic effects of axitinib and lenvatinib by inhibiting both new vasculature and mature tumor blood vessels. Xenografts that progress on axitinib monotherapy remain sensitive to the combination treatment, resulting in ∼20% tumor regression in the combination group. When tested across a panel of 18 RCC patient-derived xenograft (PDX) models, the combination induced greater antitumor effects relative to monotherapies. In this single animal study, nine out of 18 models responded with ≥50% tumor regression from baseline in the combination group. By disrupting an adaptive stress response evoked by VEGFR-TKI, HC-5404 presents a clinical opportunity to improve the antitumor effects of well-established standard-of-care therapies in RCC.

This thesis constructs a history surrounding the organization and hanging of the 1910 International Exhibition of Pictorial Photography, which was arranged by Alfred Stieglitz and the Photo-Secession for the Buffalo Fine Arts Academy at the Albright-Knox Art Gallery (then the Albright Art Gallery). This history identifies those involved in the planning and execution of the exhibition and is presented as a timeline of events revealed largely through correspondence between Stieglitz and Cornelia Sage, Director of the Albright Art Gallery. This thesis also examines in detail the installation of the 594 selected works exhibited at the Buffalo institution. In addition, this thesis project outlines the procedure of developing a small exhibition to honor the centennial anniversary of the International Exhibition of Pictorial Photography. Presented to the curatorial staff at George Eastman House International Museum of Photography and Film in Rochester, New York, the proposed exhibition is intended to hang during the 2010 calendar year.

The electrochemical CO2 reduction reaction (CO2RR) to form highly valued chemicals is a sustainable solution to address the environmental issues caused by excessive CO2 emissions. Generally, it is challenging to achieve high efficiency and selectivity simultaneously in the CO2RR due to multi-proton/electron transfer processes and complex reaction intermediates. Among the studied formulations, bimetallic catalysts have attracted significant attention with promising activity, selectivity, and stability. Engineering the atomic arrangement of bimetallic nanocatalysts is a promising strategy for the rational design of structures (intermetallic, core/shell, and phase-separated structures) to improve catalytic performance. This review summarizes the recent advances, challenges, and opportunities in developing bimetallic catalysts for the CO2RR. In particular, we firstly introduce the possible reaction pathways on bimetallic catalysts concerning the geometric and electronic properties of intermetallic, core/shell, and phase-separated structures at the atomic level. Then, we critically examine recent advances in crystalline structure engineering for bimetallic catalysts, aiming to establish the correlations between structures and catalytic properties. Finally, we provide a perspective on future research directions, emphasizing current challenges and opportunities.

We report the colloidal synthesis of quaternary kesterite CZTS-CZTSe heterostructures via anion exchange reactions on a kesterite CZTS template. The crystal phase selectivity during the synthesis (kesterite vs. wurtzite) is due to the initial nucleation of cubic Cu9S5 seeds, followed by incorporation of Zn and Sn. Upon injection of Se-precursor, which triggered simultaneous anion exchange and overgrowth of the pristine CZTS template, sandwich CZTS-CZTSe (core-tip) nanoheterostructures were obtained. X-ray photoelectron spectroscopy (XPS) and optical band gap measurement results suggest a change of intrinsic electronic structure of CZTS by Se-treatment. Our study not only provides insight into mechanisms of formation of kesterite CZTS nanocrystals (NCs) and subsequent anion exchange reactions, but also opens doors to access novel CZTSSe nanostructures for potential applications.

Solution synthesis of molecular cyanide magnets via FeSe template is promoted by thermal activation, where TCNE molecules substitute Se atoms in two-dimensional FeSe framework.

Angiogenesis is an irreplaceable therapeutic cancer target, where anti-angiogenesis are drugs that are limited by their hydrophobicity and low therapeutic effects. What is more, the long-term shutdown of tumor blood vessel density also aggravates hypoxia and causes immunosuppression in the tumor microenvironment (TME). In order to solve these shortcomings, we developed a single therapeutic agent based on a bovine serum albumin nanocarrier that can co-deliver the anti-angiogenic drug Sorafenib ("S") and the photosensitizer Ce6 ("C") along with a molecular oxygen supply based on MnO2 ("M") as a convenient one-pot formulated nanoscale agent (SCM@BSA). Compared with anti-angiogenesis monotherapy, SCM@BSA can not only improve upon the solubility and therapeutic effects of anti-angiogenesis agents, but it also reshapes the immunosuppressive TME during anti-angiogenic therapy. Together, these results point out that SCM@BSA synthesized via a very simple method can solve the shortcomings usually experienced during long-term anti-angiogenic therapy.

Reduced graphene oxide-nanoscale zero valent iron (rGO–nZVI) nanohybrid, with tunable adsorption sites of rGO and unique catalytic redox activity of nZVI, perform enhanced removal of diverse PPCPs from water.