The sensitivity of biological imaging can be significantly enhanced by near-infrared (NIR) fluorescent dyes, which offer deep tissue penetration and low background interference. However, their practical application in targeted imaging is limited by low fluorescence intensity at the sites of interest, primarily caused by restricted availability of cellular binding sites and the hydrophobic nature of most NIR dyes, leading to compromised solubility and stability in aqueous milieus. To address these challenges, we design and synthesize a series of functional fluorescent polymers using poly(pentafluorophenyl acrylate) (PPFPA) as a versatile precursor for targeted modifications. The synthesis involves the conjugation of amine-functionalized IR775 NIR dye to the reactive PFP ester units, followed by the incorporation of poly(ethylene glycol) (PEG) chains to enhance hydrophilicity and biocompatibility. By tuning the dye-to-PEG ratio, the fluorescence intensity and self-assembly behavior of the polymers are modulated, yielding spherical nanoparticles with enhanced brightness at a dye loading of 25%. Biotinylation of the fluorescent copolymers then enables their targeted binding to biotin-receptor-containing surfaces. Enhancement in fluorescence signal detection postcellular internalization is demonstrated by in vitro imaging, and an increase in tissue penetration depth is shown by employing a tissue-like phantom model, validating the use of the developed fluorescent polymers as NIR probes for advanced imaging and diagnostic applications.

CO2-derived polyhydroxyurethane (PHU), synthesized via the aminolysis of cyclic carbonate, faces limitations in replacing conventional polyurethane (PU) for color-sensitive applications due to its yellow color. In this study, we investigate, for the first time, the coloration pathways in PHU and explore the use of hydrogen peroxide (H2O2) to eliminate polymer color. Model compounds, resembling a PHU repeating unit, are prepared from CO2-derived bis(cyclic carbonate) and monoamines and then thermally aged to trace the color-forming species. Observations of the changes in Fourier-transfer infrared spectroscopy and mass spectrometry indicate multi-pathway thermal oxidation to occur at both the nitrogen-vicinal and the oxygen-vicinal methylene carbon adjacent to the urethane linkage. The changes track well with an increase in the model compound's color index as determined from UV–visible spectra, providing an explanation for PHU's susceptibility to coloration. The colored model compound and PHU are then subjected to H2O2 treatment to disrupt the conjugated carbonyl groups and thus reduce the color. Parameters, including H2O2 concentration, treatment time, and temperature, are examined for a linear PHU system, and a set of optimized treatment conditions are implemented to yield PHU with reduced color and minimal damage to its molecular structure. The decolorization method developed in this study could be extended beyond PHU to treat polymeric materials that suffer from oxidation-induced coloration issues.

The paper describes guidelines for the planning, organization,and implementation of virtual activities within a metaverse environment,aiming to familiarize students with key concepts related to hard andsoft acids and bases (HSAB) theory. The guidelines are based on experiencegained during an online lesson given in January of 2022 for 188 incomingfreshmen at a large Korean university during a week-long science program.The proposed lesson involves three parts: 1) a lecture describingHSAB theory, which was conducted on Zoom; 2) a group work activityin which students demonstrate their understanding of the lecture conceptswithin a metaverse designed on the Gather.Town platform; 3) a pairworkactivity within the same metaverse in which students team up to describethe properties and interactions of acids and bases through the creationand presentation of a poster. In end-of-program evaluations, manystudents rated their experiences with social learning in the metaverseas their favorite component of the week-long program, and the instructorswho administered the lesson indicated that the poster presentationsthat the students gave demonstrated a firm grasp of HSAB theory. Thepresent lesson may be useful to practitioners who wish to teach conceptsrelated to HSAB theory in a metaverse, such as Gather.Town.

Hypomethylating agents (HMAs), such as azacitidine and decitabine, induce cancer cell death by demethylating DNAs to promote the expression of tumor-suppressor genes. HMAs also reactivate the transcription of endogenous double-stranded RNAs (dsRNAs) that trigger the innate immune response and subsequent apoptosis via viral mimicry. However, the expression patterns of endogenous dsRNAs and their relevance in the efficacy of HMAs remain largely uninvestigated. Here, we employ amidine-conjugated spiropyran (Am-SP) to examine the dynamic expression pattern of total dsRNAs regulated by HMAs. By analyzing the bone-marrow aspirates of myelodysplastic syndrome or acute myeloid leukemia patients who received the HMAs, we find a dramatic increase in total dsRNA levels upon treatment only in patients who later benefited from the therapy. We further apply our approach in solid tumor cell lines and show that the degree of dsRNA induction correlates with the effectiveness of decitabine in most cases. Notably, when dsRNA induction is accompanied by increased expression of nc886 RNA, decitabine becomes ineffective. Collectively, our study establishes the potential application of monitoring the total dsRNA levels by a small molecule as an analytical method and a dynamic marker to predict the clinical outcome of the HMA therapy.

Protein kinase R (PKR) is an immune response protein that becomes activated by double-stranded RNAs (dsRNAs). PKR overactivation is associated with degenerative diseases with inflammation, including osteoarthritis (OA), but the dsRNA activator remains largely unknown. Here, we find that mitochondrial dsRNA (mt-dsRNA) expression and its cytosolic efflux are facilitated in chondrocytes under OA-eliciting conditions, leading to innate immune activation. Moreover, mt-dsRNAs are released to the extracellular space and activate Toll-like receptor 3 at the plasma membrane. Elevated levels of mt-dsRNAs in the synovial fluids and damaged cartilage of OA patients and in the cartilage of surgery-induced OA mice further support our data. Importantly, autophagy prevents PKR activation and protects chondrocytes from mitochondrial stress partly by removing cytosolic mtRNAs. Our study provides a comprehensive understanding of innate immune activation by mt-dsRNAs during stress responses that underlie the development of OA and suggests mt-dsRNAs as a potential target for chondroprotective intervention.

Spiropyrans are a class of photochromic compounds that feature two main isoforms, a closed spiropyran (SP) and an open merocyanine (MC), which are inter-switchable with UV and visible light. The double bond containing MC isomer has several resonance forms with different optical spectra. Consequently, the overall spectral characteristic of the spiropyran solution depends on the relative contribution of each resonance form. In addition, the reversible changes of the absorbance or fluorescence spectra of MC are dictated by the environment. By utilizing these properties, spiropyran and its derivatives have been employed to monitor a variety of molecules and ions that can alter the resonance forms of MC. In this review, we provide a comprehensive discussion on a range of species that can be detected by spiropyran including metal ions, anions, acids, solvents, and even biomolecules, the major analytical detection mechanisms involved, and the novelty of such techniques. This study establishes spiropyran as a versatile platform for the detection of both organic and inorganic target molecules.

Reactive poly(pentafluorophenyl acrylate) (PPFPA)-grafted surfaces offer a versatile platform to immobilize biomolecules. Here, we utilize PPFPA-grafted surface and double-stranded RNA (dsRNA) recognizing J2 antibody to construct a universal virus detection platform with enhanced sensitivity. PPFPA on silicon substrates is prepared, and surface hydrophilicity is modulated by partial substitution of the pentafluorophenyl units with poly(ethylene glycol). Following dsRNA antibody immobilization, the prepared surfaces can distinguish long dsRNAs from single-stranded RNAs of the same length and short dsRNAs. As long dsRNAs are common byproducts of viral transcription/replication, these surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. To increase dsRNA detection sensitivity, a two-step method is devised where the captured dsRNAs are visualized with multiple fluorophore-tagged J2 antibodies. We show that the developed platform can differentiate foreign long dsRNAs from cellular dsRNAs and other biomolecules present in the cell lysate. Moreover, when tested against cells infected with hepatitis A or C viruses, both viruses are successfully detected using a single platform. Our study shows that the developed PPFPA platform immobilized with J2 antibody can serve as a primary diagnostic tool to determine the infection status for a wide range of viruses.

Long double-stranded RNAs (dsRNAs) are duplex RNAs that can induce immune response when present in mammalian cells. These RNAs are historically associated with viral replication, but recent evidence suggests that human cells naturally encode endogenous dsRNAs that can regulate antiviral machineries in cellular contexts beyond immune response. In this study, we use photochromic organic compound spiropyran to profile and quantitate dsRNA expression. We show that the open form of spiropyran, merocyanine, can intercalate between RNA base pairs, which leads to protonation and alteration in the spectral property of the compound. By quantifying the spectral change, we can detect and quantify dsRNA expression level, both synthetic and cellular. We further demonstrate that spiropyrans can be used as a molecular diagnostic tool to profile endogenously expressed dsRNAs. Particularly, we show that spiropyrans can robustly detect elevated dsRNA levels when colorectal cancer cells are treated with 5-aza-2′-deoxycytidine, an FDA-approved DNA-demethylating agent used for chemotherapy, thus demonstrating the use of spiropyran for predicting responsiveness to the drug treatment. As dsRNAs are signature of virus and accumulation of dsRNAs is implicated in various degenerative disease, our work establishes potential application of spiropyrans as a simple spectral tool to diagnose human disease based on dsRNA expression.

We demonstrate a simple method to prepare poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads for antibody immobilization and subsequent immunoprecipitation (IP) application. The poly(PFPA) grafted surface is prepared via a simple two-step process. In the first step, 3-aminopropyltriethoxysilane (APTES) is deposited as a linker molecule onto the silica surface. In the second step, poly(PFPA) homopolymer, synthesized via the reversible addition and fragmentation chain transfer (RAFT) polymerization, is grafted to the linker molecule through the exchange reaction between the pentafluorophenyl (PFP) units on the polymer and the amine groups on APTES. The deposition of APTES and poly(PFPA) on the silica particles are confirmed by X-ray photoelectron spectroscopy (XPS), as well as monitored by the particle size change measured via dynamic light scattering (DLS). To improve the surface hydrophilicity of the beads, partial substitution of poly(PFPA) with amine-functionalized poly(ethylene glycol) (amino-PEG) is also performed. The PEG-substituted poly(PFPA) grafted silica beads are then immobilized with antibodies for IP application. For demonstration, an antibody against protein kinase RNA-activated (PKR) is employed, and IP efficiency is determined by Western blotting. The analysis results show that the antibody immobilized beads can indeed be used to enrich PKR while non-specific protein interactions are minimal.

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1(2)-Aryl-5-methylsulfonyltetrazoles react with ethylene glycol, di- and triethylene glycols, and tris(2-hydroxyethyl)amine in acetonitrile in the presence of sodium hydroxide to give tetrazole-containing ethers. The products can be used as polydentate ligands for biomimetic studies.