An Activatable NIR-II Nanoprobe for In Vivo Early Real-Time Diagnosis of Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the most dangerous acute diseases resulting in high morbidity and mortality. Current methods remain limited with respect to early diagnosis and real-time feedback on the pathological process. Herein, a targeted activatable fluorescent nanoprobe (V&A@Ag₂S) in the second near-infrared window (NIR-II) is presented for in vivo optical imaging of TBI. Initially, the fluorescence of V&A@Ag₂S is turned off owing to energy transfer from Ag₂S to the A1094 chromophore. Upon intravenous injection, V&A@Ag₂S quickly accumulates in the inflamed vascular endothelium of TBI based on VCAM1-mediated endocytosis, after which the nanoprobe achieves rapid recovery of the NIR-II fluorescence of Ag₂S quantum dots (QDs) owing to the bleaching of A1094 by the prodromal biomarker of TBI, peroxynitrite (ONOO⁻). The nanoprobe offers high specificity, rapid response, and high sensitivity toward ONOO⁻, providing a convenient approach for in vivo early real-time assessment of TBI.     

A Generalizable and Noncovalent Strategy for Interfacing Aptamers with a Microelectrode for the Selective Sensing of Neurotransmitters In Vivo

The selective sensing of neurochemicals is essential for understanding the chemical basis of brain function and pathology. Interfacing the excellent recognition features of aptamers with in vivo compatible carbon fiber microelectrode (CFE)-based electroanalytical systems offers a plausible means to achieve this end. However, this is challenging in terms of coupling chemistry, stability, and versatility. Here, we present a new interfacial functionalization strategy based on the assembly of aptamer cholesterol amphiphiles (aptCAs) on the alkyl chain-functionalized CFE. The noncovalent cholesterol-alkyl chain interactions effectively immobilize aptamers onto the CFE surface, allowing the generation of a highly selective system for probing neurochemical dynamics in living systems and opening up a vast array of new opportunities for designing in vivo sensors for exploring brain chemistry.     

A Fluorescent Probe for Rapid,High-Contrast Visualization of Folate-Receptor-Expressing Tumors In Vivo

Folate receptors (FRs) are membrane proteins involved in folic acid uptake, and the alpha isoform (FR-α) is overexpressed in ovarian and endometrial cancer cells. For fluorescence imaging of FRs in vivo, the near-infrared (NIR) region (650–900 nm), in which tissue penetration is high and autofluorescence is low, is optimal, but existing NIR fluorescent probes targeting FR-α show high non-specific tissue adsorption, and require prolonged washout to visualize tumors. We have designed and synthesized a new NIR fluorescent probe, FolateSiR-1 , utilizing a Si-rhodamine fluorophore having a carboxy group at the benzene moiety, coupled to a folate ligand moiety through a negatively charged tripeptide linker. This probe exhibits very low background fluorescence and afforded a tumor-to-background ratio (TBR) of up to 83 in FR-expressing tumor-bearing mice within 30 min. Thus, FolateSiR-1 has the potential to contribute to the research in the field of biology and the clinical medicine.     

Versatile Fluorescent Probes for Imaging the Superoxide Anion in Living Cells and In Vivo

The superoxide anion (O₂^.−) is widely engaged in the regulation of cell functions and is thereby intimately associated with the onset and progression of many diseases. To ascertain the pathological roles of O₂^.− in related diseases, developing effective methods for monitoring O₂^.− in biological systems is essential. Fluorescence imaging is a powerful tool for monitoring bioactive molecules in cells and in vivo owing to its high sensitivity and high temporal-spatial resolution. Therefore, increasing numbers of fluorescent imaging probes have been constructed to monitor O₂^.− inside live cells and small animals. In this minireview, we summarize the methods for design and application of O₂^.−-responsive fluorescent probes. Moreover, we present the challenges for detecting O₂^.− and suggestions for constructing new fluorescent probes that can indicate the production sites and concentration changes in O₂^.− as well as O₂^.−-associated active molecules in living cells and in vivo.     

In Vivo Imaging of the Tumor-Associated Enzyme NCEH1 with a Covalent PET Probe

Herein, we report the development of an ¹⁸F-labeled, activity-based small-molecule probe targeting the cancer-associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile ¹⁸F radionuclide incorporation required for PET imaging. The resulting molecule, [¹⁸F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000-fold selectivity relative to other serine hydrolases. [¹⁸F]JW199 displays rapid, NCEH1-dependent accumulation in mouse tissues. Finally, we demonstrate that [¹⁸F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple-negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis.     

Is sarcosine a biomarker for prostate cancer?

Sarcosine was suggested in a letter to Nature in 2009 as a biomarker for prostate cancer. This communication reviews what has been accomplished to date to determine whether sarcosine is or is not a biomarker for prostate cancer that can replace prostate-specific antigen tests.     

In Vivo Solid-Phase Microextraction for Sampling of Oxylipins in Brain of Awake,Moving Rats

Oxylipins are key lipid mediators of important brain processes, including pain, sleep, oxidative stress, and inflammation. For the first time, an in-depth profile of up to 52 oxylipins can be obtained from the brains of awake moving animals using in vivo solid-phase microextraction (SPME) chemical biopsy tool in combination with liquid chromatography–high resolution mass spectrometry. Among these, 23 oxylipins are detectable in the majority of healthy wildtype samples. This new approach successfully eliminates the changes in oxylipin concentrations routinely observed during the analysis of post-mortem samples, allows time-course monitoring of their concentrations with high spatial resolution in specific brain regions of interest, and can be performed using the same experimental set-up as in vivo microdialysis (MD) thus providing a new and exciting tool in neuroscience and drug discovery.     

Ginger,a Possible Candidate for the Treatment of Dementias?

As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer’s Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer’s Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.     

Is Chromatography a Science, a Process, a Method, or a Scientific Discipline?

In the controversy over an article entitled Chromatography as a Scientific Discipline by V.G. Berezkin, it was pointed out that the subdivision of chromatographic processes into sorption–sieve chromatography and field nonsorption chromatography is inadmissible. It was demonstrated that all chromatographic processes, including flow fractionation in a transverse force field, are in principle two-phase (or polyphase) processes. It was illustrated that a longitudinal field in a flow cannot introduce a chromatographic component into the system. An additional definition of chromatography as a phenomenon was proposed on the basis of key points revealed by Professor Berezkin.     

Is there a unique melting temperature for two-state proteins?

Thermal unfolding (or folding) in many proteins occurs in an apparent two-state manner, suggesting that only two states, unfolded and folded, are populated. At the melting temperature, Tm, the two states coexist. Using lattice models with side chains we show that individual residues become structured at temperatures that deviate from Tm, which implies that partially folded conformations make substantial contribution to thermodynamic properties of two-state proteins. We also find that the folding cooperativity for a given residue is linked to its accessible surface area. These results are consistent with the experiments on GCN4-like zipper peptide, which showed that local melting temperatures differ from Tm. Analysis of thermal unfolding of six proteins shows that deltaT/Tm approximately N(-1), where deltaT is the transition width and N is the number of residues. This scaling allows us to conclude that, when corrected for finite size effects, folding cooperativity can be captured using coarse grained models.     

Is there a general rule for the gauche effect in the conformational isomerism of 1,2-disubstituted ethanes?

The stabilities of the gauche and anti conformations of butane, 1,2-dicyanoethane (DCE), and 1,2-dinitroethane (DNE) have been investigated through theoretical calculations. The gauche effect-the tendency of keeping close vicinal electronegative substituents (thetaX-C-C-X approximately 60 degrees ) in an ethane fragment-is expected to drive the conformational equilibrium of DCE and DNE toward the gauche conformation. It was found that, for butane, where the gauche effect is supposed to be poor/null, the hyperconjugation effect contributes mostly to the anti stabilization in opposition to the traditional sense that the methyl groups repel each other, and this should govern its conformational equilibrium. For DCE the equilibrium was shifted to the anti conformer, essentially due to a gauche repulsion, while for DNE, despite the higher electronic delocalization energies, a predominance of the gauche conformer was obtained, and this was attributed mainly to the attractive dipolar interaction between the two nitro groups. A full orbital energy analysis was performed using the natural bond orbital approach, which showed that bond bending and anti-C-H/C-X* hyperconjugation models, usually applied to explain the origin of the gauche effect in fluorinated derivatives, are not adequate to completely explain the conformational behavior of the titled compounds.