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RNA interference (RNAi) is a powerful tool capable of targeting virtually any protein without time-consuming and expensive drug development studies. However, due to obstacles facing efficient and safe delivery, RNAi-based therapeutic approach remains a challenge. Herein, we have designed and synthesized a number of disulfide-constraining cyclic and hybrid peptides using tryptophan and arginine residues. Our hypothesis was that peptide structures would undergo reduction by intracellular glutathione (more abundant in cancer cells) and unpack the small interfering RNA (siRNA) from the peptide/siRNA complexes. A subset of newly developed peptides (specifically, C4 and H4) exhibited effective cellular internalization of siRNA (∼70% of the cell population; monitored by flow cytometry and confocal microscopy), the capability of protecting siRNA against early degradation by nucleases (monitored by gel electrophoresis), minimal cytotoxicity in selected cell lines (studied by cell viability and LC50 calculations), and efficient protein silencing by 70-75% reduction in the expression of targeting signal transducer and activator of transcription 3 (STAT3) in human triple-negative breast cancer (TNBC) MDA-MB-231 cells, analyzed using the Western blot technique. Our results indicate the birth of a promising new family of siRNA delivery systems that are capable of safe and efficient delivery, even in the presence of nucleases.Atomically thin two-dimensional (2D) materials have gained significant attention from the research community in the fabrication of high-performance optoelectronic devices. TyrphostinB42 Even though there are various techniques to improve the responsivity of the photodetector, the key factor limiting the performance of the photodetectors is constrained photodetection spectral range in the electromagnetic spectrum. In this work, a mixed-dimensional 0D/2D SnS2-QDs/monolayer MoS2 hybrid is fabricated for high-performance and broadband (UV-visible-near-infrared (NIR)) photodetector. Monolayer MoS2 is deposited on SiO2/Si using chemical vapor deposition (CVD), and SnS2-QDs are prepared using a low-cost solution-processing method. The high performance of the fabricated 0D/2D photodetector is ascribed to the band bending and built-in potential created at the junction of SnS2-QDs and MoS2, which enhances the injection and separation efficiency of the photoexcited charge carriers. The mixed-dimensional structure also suppresses the dark current of the photodetector. The decorated SnS2-QDs on monolayer MoS2 not only improve the performance of the device but also extends the spectral range to the UV region. Photoresponsivity of the device for UV, visible, and NIR region is found to be ∼278, ∼ 435, and ∼189 A/W, respectively. Fabricated devices showed maximum responsivity under the visible region attributed to the high absorbance of monolayer MoS2. The response time of the fabricated device is measured as ∼100 ms. These results reveal that the development of a mixed-dimensional (0D/2D) SnS2-QDs/MoS2-based high-performance and broadband photodetector is technologically promising for next-generation optoelectronic applications.Flufenamic acid (FFA) is a highly polymorphic drug molecule with nine crystal structures reported in the Cambridge Structural Database. This study explores the use of synchrotron X-ray powder diffraction combined with differential scanning calorimetry to study crystallization and polymorphic phase transitions upon heating FFA-polymer amorphous solid dispersions (ASDs). Ethyl cellulose (EC, 4 cp) and hydroxypropylmethylcellulose (HPMC) grades with different viscosities and substitution patterns were used to prepare dispersions with FFA at 51, 21, 11, and 15 w/w drug/polymer ratios by quench cooling. We employed a 6 cp HPMC 2910 material and two HPMC 2208 samples at 4000 and 100 000 cp. Hyphenated X-ray diffraction (XRD)-differential scanning calorimetry (DSC) studies show that the 6 and 100 000 cp HPMCs and 4 cp EC polymers can stabilize FFA form IV by inhibiting the transition to form I during heating. It appears that the polymers stabilize FFA in both amorphous and metastable forms via a combination of intermolecular interactions and viscosity effects. Increasing the polymer content of the ASD also inhibits polymorphic transitions, with drug/polymer ratios of 15 w/w resulting in FFA remaining amorphous during heating. The comparison of FFA ASDs prepared with different samples of HPMCs and ECs suggests that the chemical substitution of the polymer (HPMC 2208 has 19-24% methoxy groups and 4-12% hydroxypropyl groups, while HPMC 2910 has 28-30% methoxy groups and 7-12% hydroxypropyl groups) plays a more significant role in directing polymorphic transitions than the viscosity. A previously unreported polymorph of FFA was also noted during heating but its structure could not be determined.Protein-protein interactions often rely on specialized recognition domains, such as WW domains, which bind to specific proline-rich sequences. The specificity of these protein-protein interactions can be increased by tandem repeats, i.e., two WW domains connected by a linker. With a flexible linker, the WW domains can move freely with respect to each other. Additionally, the tandem WW domains can bind in two different orientations to their target sequences. This makes the elucidation of complex structures of tandem WW domains extremely challenging. Here, we identify and characterize two complex structures of the tandem WW domain of human formin-binding protein 21 and a peptide sequence from its natural binding partner, the core-splicing protein SmB/B’. The two structures differ in the ligand orientation and, consequently, also in the relative orientation of the two WW domains. We analyze and probe the interactions in the complexes by molecular simulations and NMR experiments. The workflow to identify the complex structures uses molecular simulations, density-based clustering, and peptide docking. It is designed to systematically generate possible complex structures for repeats of recognition domains. These structures will help us to understand the synergistic and multivalency effects that generate the astonishing versatility and specificity of protein-protein interactions.During photon upconversion, quantum dots (QDs) transfer energy to molecules in solution through a long ligand shell. This insulating ligand shell imparts colloidal stability at the expense of efficient photosensitization. For the first time, we quantify the barrier these aliphatic ligands pose for triplet energy transfer in solution. Using transient absorption spectroscopy, we experimentally measure a small damping coefficient of 0.027 Å-1 for a ligand exceeding 10 carbons in length. The dynamic nature of ligands in solution lowers the barrier to charge or energy transfer compared to organic thin films. In addition, we show that surface ligands shorter than 8 carbons in length allow direct energy transfer from the QD, bypassing the need for a transmitter ligand to mediate energy transfer, leading to a 6.9% upconversion quantum yield compared with 0.01% for ligands with 18 carbons. This experimentally derived insight will enable the design of efficient QD-based photosensitizers for catalysis and energy conversion.A chemical study on the epidermis of cultivated edible mushroom Wolfiporia cocos resulted in the isolation and identification of 46 lanostane triterpenoids, containing 17 new compounds (1-17). An experimental determination of their anti-inflammatory activity showed that poricoic acid GM (39) most strongly inhibited NO production in LPS-induced RAW264.7 murine macrophages with an IC50 value at 9.73 μM. Furthermore, poricoic acid GM induced HO-1 protein expression and inhibited iNOS and COX2 protein expression as well as the release of PGE2, IL-1β, IL-6, TNF-α, and reactive oxygen species (ROS) in LPS-induced RAW264.7 cells. Mechanistically, poricoic acid GM suppressed the phosphorylation of the IκBα protein, which prevented NF-κB from entering the nucleus to lose transcriptional activity and inhibited the dissociation of Keap1 from Nrf2, thereby activating Nrf2 into the nucleus to regulate antioxidant genes. Furthermore, the MAPK signaling pathway may play a significant role in poricoic acid GM-induced elimination of inflammation. This work further confirms that lanostane triterpenoids are key ingredients responsible for the anti-inflammatory properties of the edible medicinal mushroom W. cocos.The interplay between the primary and secondary coordination spheres in biological metal sites plays an essential role in controlling their properties. Some of the clearest examples of this are from copper sites in blue and purple copper proteins. Many such proteins contain methionine (Met) in the primary coordination sphere as a weakly bound ligand to Cu. While the effects of replacing the coordinated Met are understood, less so is the importance of its second-sphere interactions. In this combined informatics and experimental study, we first present a bioinformatics investigation of the second-sphere environments in biological Met-Cu motifs. The most common interaction is between the Met-CH3 and the π-face of a phenylalanine (Phe) (81% of surveyed structures), tyrosine (Tyr) (11%), and tryptophan (Trp) (8%). In most cases, the Met-CH3 also forms a contact with a π-face of one of a Cu-ligating histidine-imidazole. Such interactions are widely distributed in different Cu proteins. Second, to explore the impact of the second-sphere interactions of Met, a series of artificial Pseudomonas aeruginosa azurin proteins were produced where the native Phe15 was replaced with Tyr or Trp. The proteins were characterized using optical and magnetic resonance spectroscopies, X-ray diffraction, electrochemistry, and an investigation of the time-resolved electron-transfer kinetics of photosensitizer-modified proteins. The influence of the Cu-Met-Aro interaction on azurin’s physical properties is subtle, and the hallmarks of the azurin blue copper site are maintained. In the Phe15Trp variant, the mutation to Phe15 induces changes in Cu properties that are comparable to replacement of the weak Met ligand. The broader impacts of these widely distributed interactions are discussed.Multiple analytical techniques were combined to achieve a detailed characterization of organic residues in different typologies of funerary pottery, which were found at two separate archeological sites in the Campania Region (Italy) and both dated back to the first millennium BC. Gas chromatography-mass spectrometry (GC-MS) analysis of lipids provided inconclusive results. The attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra of encrustation on two glazed bowls of the 3rd to 4th century BC were comparable to those of fresh bone, revealing the presence of hydroxyapatite and proteins, which were identified as bovine collagen chains by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS)-based proteomics. This finding confirmed that Italic populations used to inhume the dead along with votive meat offerings. Proteomics was decisive for identifying bovine milk in an unusually shaped amphora unearthed from a grave that belonged to a woman at the necropolis of the Greek colony in Cuma (7th century BC).