Chemiluminescence imaging is imperative for diagnostics and imaging due to its intrinsically high sensitivity. To improve in vivo detection of biomarkers, chemiluminophores that simultaneously possess near-infrared (NIR) emission and modular structures amenable to construction of activatable probes are highly desired; however, these are rare. Herein, we report two chemiluminophores with record long NIR emission (>750 nm) via integration of dicyanomethylene-4H-benzothiopyran or dicyanomethylene-4H-benzoselenopyran with dioxetane unit. Caging of the chemiluminophores with different cleavable moieties produces NIR chemiluminescence probes (NCPs) that only produce signals upon reaction with reactive oxygen species or enzymes, for example, β-galactosidase, with a tissue-penetration depth of up to 2 cm. Thus, this study provides NIR chemiluminescence molecular scaffolds applicable for in vivo turn-on imaging of versatile biomarkers in deep tissues.

Molecular Chemiluminescent Probes with a Very Long Near-Infrared Emission Wavelength for in Vivo Imaging

The COVID-19 pandemic is a global threat presenting health, economic, and social challenges that continue to escalate. Metapopulation epidemic modeling studies in the susceptible-exposed-infectious-removed (SEIR) style have played important roles in informing public health policy making to mitigate the spread of COVID-19. These models typically rely on a key assumption on the homogeneity of the population. This assumption certainly cannot be expected to hold true in real situations; various geographic, socioeconomic, and cultural environments affect the behaviors that drive the spread of COVID-19 in different communities. What's more, variation of intracounty environments creates spatial heterogeneity of transmission in different regions. To address this issue, we develop a human mobility flow-augmented stochastic SEIR-style epidemic modeling framework with the ability to distinguish different regions and their corresponding behaviors. This modeling framework is then combined with data assimilation and machine learning techniques to reconstruct the historical growth trajectories of COVID-19 confirmed cases in two counties in Wisconsin. The associations between the spread of COVID-19 and business foot traffic, race and ethnicity, and age structure are then investigated. The results reveal that, in a college town (Dane County), the most important heterogeneity is age structure, while, in a large city area (Milwaukee County), racial and ethnic heterogeneity becomes more apparent. Scenario studies further indicate a strong response of the spread rate to various reopening policies, which suggests that policy makers may need to take these heterogeneities into account very carefully when designing policies for mitigating the ongoing spread of COVID-19 and reopening.

https://www.pnas.org/content/pnas/118/24/e2020524118.full.pdf

Intracounty modeling of COVID-19 infection with human mobility: Assessing spatial heterogeneity with business traffic, age, and race.

Skin-inspired gelatin-based flexible bio-electronic hydrogel for wound healing promotion and motion sensing.

Worldwide, Alzheimer's disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

Curcumin in Health and Diseases: Alzheimer's Disease and Curcumin Analogues, Derivatives, and Hybrids.

Since its birth in 1967, the utilization of chemiluminescence resonance energy transfer (CRET) has made substantial progress in a variety of fields for its unique features. However, the quantitative relationship between CRET efficiency and donor-acceptor distance has not yet been determined owing to the difficulty in designing the variable lengths between chemiluminescent donors and acceptors. Herein, we synthesized three kinds of tetraphenylethene (TPE)-anchored cationic surfactants with aggregation-induced emission (AIE) characteristics. For the first time, it is quantitatively demonstrated that the CRET efficiency is inversely proportional to the sixth power of distance between luminol donors and TPE acceptors. The details disclosed in this contribute have provided the solid evidence that CRET follows Forster resonance theory. Our strategy would build a promising platform to control donor-acceptor distance, allowing to the interdisciplinary applications of CRET.

Chemiluminescence Resonance Energy Transfer Efficiency and Donor-Acceptor Distance: from Qualitative to Quantitative.

Turn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood–brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins. Detection of amyloid beta deposits is often performed with fluorescent compounds that bind plaques. Here the authors develop turn-on chemiluminescent probes that bind amyloid beta plaques in vivo, and amplify the signal via chemiluminescence resonance energy transfer to the plaque-binding fluorescent molecule CRANAD-3.

/pdf/turn-on-chemiluminescence-probes-and-dual-amplification-of-3kg3p710yj.pdf

Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo.

Half-curcumin analogues as PET imaging probes for amyloid beta species

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Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo.

Half-curcumin analogues as PET imaging probes for amyloid beta species