Brochfernandez4773

The use of a bulk heterojunction of organic semiconductors to drive photoelectrochemical water splitting is an emerging trend; however, the optimum energy levels of the donor and acceptor have not been established for photoanode operation with respect to electrolyte pH. Herein, we prepare a set of donor polymers and non-fullerene acceptors with varying energy levels to probe the effect of photogenerated electron injection into a SnO2-based substrate under sacrificial photo-oxidation conditions. Photocurrent density (for sacrificial oxidation) up to 4.1 mA cm-2 was observed at 1.23 V vs reversible hydrogen electrode in optimized photoanodes. Moreover, we establish that a lower-lying donor polymer leads to improved performance due to both improved exciton separation and better charge collection. Similarly, lower-lying acceptors also give photoanodes with higher photocurrent density but with a later photocurrent onset potential and a narrower range of pH for good operation due to the Nernstian behavior of the SnO2, which leads to a smaller driving force for electron injection at high pH.Coiled coils are among the most abundant tertiary and quaternary structures found in proteins. A growing body of evidence suggests that long-range synergistic interactions among solvent-exposed residues can contribute substantially to coiled-coil conformational stability, but our understanding of the key sequence and structural prerequisites of this effect is still developing. Here, we show that the strength of synergistic interaction involving a b-position Glu (i), an f-position Tyr (i + 4), and a c-position Lys (i + 8) depends on the identity of the f-position residue, the length and stability of the coiled coil, and its oligomerization stoichiometry/surface accessibility. Combined with previous observations, these results map out predictable sequence- and structure-based criteria for enhancing coiled-coil stability by up to -0.58 kcal/mol per monomer (or -2.32 kcal/mol per coiled-coil tetramer). Our observations expand the available tools for enhancing coiled coil stability by sequence variation at solvent-exposed b-, c-, and f-positions and suggest the need to exercise care in the choice of substitutions at these positions for application-specific purposes.Combination chemotherapy has become a treatment modality for breast cancer. However, serious side effects and high cytotoxicity associated with this combination therapy make it a high-risk method for breast cancer treatment. This study evaluated the anticancer effect of decorated niosomal nanocarriers loaded with cisplatin (CIS) and epirubicin (EPI) in vitro (on SKBR3 and 4T1 breast cancer cells) and in vivo on BALB/c mice. For this purpose, polyethylene glycol (PEG) and folic acid (FA) were employed to prepare a functionalized niosomal system to improve endocytosis. FA-PEGylated niosomes exhibited desired encapsulation efficiencies of ∼91.2 and 71.9% for CIS and EPI, respectively. Moreover, cellular assays disclosed that a CIS and EPI-loaded niosome (NCE) and FA-PEGylated niosomal CIS and EPI (FPNCE) enhanced the apoptosis rate and cell migration in SKBR3 and 4T1 cells compared to CIS, EPI, and their combination (CIS+EPI). For FPNCE and NCE groups, the expression levels of Bax, Caspase3, Caspase9, and Mfn1 genes increased, whereas the expression of Bcl2, Drp1, MMP-2, and MMP-9 genes was downregulated. Histopathology results showed a reduction in the mitosis index, invasion, and pleomorphism in BALB/c inbred mice with NCE and FPNCE treatment. In this paper, for the first time, we report a niosomal nanocarrier functionalized with PEG and FA for codelivery of CIS and EPI to treat breast cancer. The results demonstrated that the codelivery of CIS and EPI through FA-PEGylated niosomes holds great potential for breast cancer treatment.Early detection of human neutrophil elastase (HNE), the potential biomarker of lung cancer, is crucial for the accurate diagnosis and evaluation of lung cancer. Currently, little progress of HNE-activated probes has been made for in vivo imaging. Herein, assisted by probe-active pocket match engineering, we synthesized a series of near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging probes by conjugating diverse fluorinated amide chains onto hemi-cyanine. Finally, we identified that probe 2 (denoted as LET-8), with the pentafluoroethyl group, is a superior probe to detect HNE with the best selectivity as well as good response ability and thus successfully realized NIRF/PA duplex imaging of HNE activity both in vitro and in vivo.Chemically stable chromenoquinoline (CQ)-based covalent organic frameworks (COFs) were constructed by postsynthetic conversion of imine COFs. The key step of an intramolecular Povarov reaction can transform a preintegrated alkyne group to bridge the benzene rings on both sides of the imine linkage via chemical bonds, affording a ladder-type CQ linkage. This novel approach achieves a high cyclization degree of 80-90%, which endows the CQ-COFs with excellent chemical stability toward strong acid, base, and redox reagents. The synthetic approach can be applied to various monomers with different symmetries and functional core moieties. The absorption and fluorescence intensities of CQ-COFs are sensitive to acid, which allows for dual-mode sensing of strongly acidic environments.Structural proteins are the basis of many biomaterials and key construction and functional components of all life. Further, it is well-known that the diversity of proteins' function relies on their local structures derived from their primary amino acid sequences. Here, we report a deep learning model to predict the secondary structure content of proteins directly from primary sequences, with high computational efficiency. Understanding the secondary structure content of proteins is crucial to designing proteins with targeted material functions, especially mechanical properties. Using convolutional and recurrent architectures and natural language models, our deep learning model predicts the content of two essential types of secondary structures, the α-helix and the β-sheet. 8Cyclopentyl1,3dimethylxanthine The training data are collected from the Protein Data Bank and contain many existing protein geometries. We find that our model can learn the hidden features as patterns of input sequences that can then be directly related to secondary structure content. The α-helix and β-sheet content predictions show excellent agreement with training data and newly deposited protein structures that were recently identified and that were not included in the original training set. We further demonstrate the features of the model by a search for de novo protein sequences that optimize max/min α-helix/β-sheet content and compare the predictions with folded models of these sequences based on AlphaFold2. Excellent agreement is found, underscoring that our model has predictive potential for rapidly designing proteins with specific secondary structures and could be widely applied to biomedical industries, including protein biomaterial designs and regenerative medicine applications.Albumin-nucleic acid biomolecular drug designs offer modular multifunctionalization and extended circulatory half-life. However, stability issues associated with conventional DNA nucleotides and maleimide bioconjugation chemistries limit the clinical potential. This work aims to improve the stability of this thiol conjugation and nucleic acid assembly by employing a fast-hydrolyzing monobromomaleimide (MBM) linker and nuclease-resistant nucleotide analogues, respectively. The biomolecular constructs were formed by site-selective conjugation of a 12-mer oligonucleotide to cysteine 34 (Cys34) of recombinant human albumin (rHA), followed by annealing of functionalized complementary strands bearing either a fluorophore or the cytotoxic drug monomethyl auristatin E (MMAE). Formation of conjugates and assemblies was confirmed by gel shift analysis and mass spectrometry, followed by investigation of serum stability, neonatal Fc receptor (FcRn)-mediated cellular recycling, and cancer cell killing. The MBM linker afforded rapid conjugation to rHA and remained stable during hydrolysis. The albumin-nucleic acid biomolecular assembly composed of stabilized oligonucleotides exhibited high serum stability and retained FcRn engagement mediating FcRn-mediated cellular recycling. The MMAE-containing assembly exhibited cytotoxicity in the human MIA PaCa-2 pancreatic cancer cell line with an IC50 of 342 nM, triggered by drug release from breakdown of an acid-labile linker. In summary, this work presents rHA-nucleic acid module-based assemblies with improved stability and retained module functionality that further promotes the drug delivery potential of this biomolecular platform.The Minamata Convention on Mercury calls for Hg control actions to protect the environment and human beings from the adverse impacts of Hg pollution. It aims at the entire life cycle of Hg. Existing studies on the Hg cycle in the global environmental-economic system have characterized the emission-to-impact pathway of Hg pollution. That is, Hg emissions/releases from the economic system can have adverse impacts on human health and ecosystems. However, current modeling of the Hg cycle is not fully looped. It ignores the feedback of Hg-related environmental impacts (including human health impacts and ecosystem impacts) to the economic system. This would impede the development of more comprehensive Hg control actions. By synthesizing recent information on Hg cycle modeling, this critical review found that Hg-related environmental impacts would have feedbacks to the economic system via the labor force and biodiversity loss. However, the interactions between Hg-related activities in the environmental and economic systems are not completely clear. The cascading effects of Hg-related environmental impacts to the economic system throughout global supply chains have not been revealed. Here, we emphasize the knowledge gaps and propose possible approaches for looping the Hg cycle in global environmental-economic system modeling. This progress is crucial for formulating more dynamic and flexible Hg control measures. It provides new perspectives for the implementation of the Minamata Convention on Mercury.Site-specific modification of proteins has important applications in biological research and drug development. Reactive tags such as azide, alkyne, and tetrazine have been used extensively to achieve the abovementioned goal. However, bulky side-chain "ligation scars" are often left after the labeling and may hinder the biological application of such engineered protein products. Conjugation chemistry via dehydroalanine (Dha) may provide an opportunity for "traceless" ligation because the activated alkene moiety on Dha can then serve as an electrophile to react with radicalophile, thiol/amine nucleophile, and reactive phosphine probe to introduce a minimal linker in the protein post-translational modifications. In this report, we present a mild and highly efficient enzymatic approach to incorporate Dha with phosphothreonine/serine lyases, OspF and SpvC. These lyases originally catalyze an irreversible elimination reaction that converts a doubly phosphorylated substrate with phosphothreonine (pT) or phosphoserine (pS) to dehydrobutyrine (Dhb) or Dha.