BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer.
RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation.
CONCLUSIONS: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

BACKGROUND: Cirrhosis represents the terminal stage of liver disease progression and timely intervention in a diseased liver can enhance the likelihood of recovery. Viscosity, a crucial parameter of the cellular microenvironment, is intricately linked to the advancement of cirrhosis. However, viscosity monitoring still faces significant challenges in achieving non-invasive and rapid early diagnosis of cirrhosis. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, non-destructive detection, and ignoring background fluorescence interference, plays an important role in diagnosing and treating various biological diseases. Hence, monitoring cellular viscosity changes with NIR fluorescence probe holds great significance in the early diagnosis of cirrhosis.
RESULTS: In this study, the NIR fluorescence probe based on the intramolecular charge transfer (TICT) mechanism was developed for imaging applications in mouse model of liver cirrhosis. A molecular rotor-type viscosity-responsive probe was synthesized by linking dioxanthracene groups via carbon-carbon double bonds. The probe demonstrated remarkable sensitivity, high selectivity and photostability, with its responsiveness to viscosity largely unaffected by factors such as polarity, pH, and interfering ions. The probe could effectively detect various drug-induced changes in cellular viscosity, enabling the differentiation between normal cells and cancerous cells. Furthermore, the enhanced tissue penetration capabilities of probe facilitated its successful application in mouse model of liver cirrhosis, allowing for the assessment of liver disease severity based on fluorescence intensity and providing a powerful tool for early diagnosis of cirrhosis.
CONCLUSIONS: A NIR viscosity-sensitive fluorescent probe was specifically designed to effectively monitor alterations in cellular and organ viscosity, which could advance the understanding of the biological characteristics of cancer and provide theoretical support for the early diagnosis of cirrhosis. Overall, this probe held immense potential in monitoring viscosity-related conditions, expanding the range of biomedical tools available.

Fluorescence analysis has been regarded as one of the commonly used analytical methods because of its advantages of simple operation, fast response, low cost and high sensitivity. So far, various fluorescent probes, with noble metal nanoclusters, quantum dots, organic dyes and metal organic frameworks as representatives, have been widely reported. However, single fluorescent probe often suffers from some deficiencies, such as low quantum yield, poor chemical stability, low water solubility and toxicity. To overcome these disadvantages, the introduction of cyclodextrins into fluorescent probes has become a fascinating approach. This review (with 218 references) systematically covers the research progress of fluorescent composites based on cyclodextrins in recent years. Preparation strategies, fluorescence properties, response mechanisms and applications in sensing (ions, organic pollutants, bio-related molecules, temperature, pH) and bioimaging of fluorescent composites based on cyclodextrins are summarized in detail. Finally, the current challenges and future perspectives of these composites in relative research fields are discussed.

Recent years have witnessed a surge of interest in tuning the optical properties of organic semiconductors for diverse applications. However, achieving control over the optical bandgap in the second near-infrared (NIR-II) window has remained a major challenge. To address this, here we report a polaron engineering strategy that introduces diverse defects into carbon quantum dots (CQDs). These defects induce lattice distortions resulting in the formation of polarons, which can absorb the near-field scattered light. Furthermore, the formed polarons in N-related vacancies can generate thermal energy through the coupling of lattice vibrations, while the portion associated with O-related defects can return to the ground state in the form of NIR-II fluorescence. On the basis of this optical absorption model, these CQDs have been successfully applied to NIR-II fluorescence imaging and photothermal therapy. This discovery could open a promising route for the polarons of organic semiconductor materials as NIR-II absorbers in nanomedical applications.

Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.

UNASSIGNED: Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) provides a label-free approach to observe functional and molecular changes at cellular scale in vivo. Adding multispectral capabilities improves interpretation of lifetime fluctuations due to individual fluorophores in the retinal pigment epithelium (RPE).
UNASSIGNED: To quantify the cellular-scale changes in autofluorescence with age and eccentricity due to variations in lipofuscin, melanin, and melanolipofuscin in RPE using multispectral AOFLIO.
UNASSIGNED: AOFLIO was performed on six subjects at seven eccentricities. Four imaging channels ( λ ex / λ em ) were used: 473/SSC, 473/LSC, 532/LSC, and 765/NIR. Cells were segmented and the timing signals of each pixel in a cell were combined into a single histogram, which were then used to compute the lifetime and phasor parameters. An ANOVA was performed to investigate eccentricity and spectral effects on each parameter.
UNASSIGNED: A repeatability analysis revealed < 11.8 % change in lifetime parameters in repeat visits for 532/LSC. The 765/NIR and 532/LSC had eccentricity and age effects similar to previous reports. The 473/LSC had a change in eccentricity with mean lifetime and a phasor component. Both the 473/LSC and 473/SSC had changes in eccentricity in the short lifetime component and its relative contribution. The 473/SSC had no trend in eccentricity in phasor. The comparison across the four channels showed differences in lifetime and phasor parameters.
UNASSIGNED: Multispectral AOFLIO can provide a more comprehensive picture of changes with age and eccentricity. These results indicate that cell segmentation has the potential to allow investigations in low-photon scenarios such as in older or diseased subjects with the co-capture of an NIR channel (such as 765/NIR) with the desired spectral channel. This work represents the first multispectral, cellular-scale fluorescence lifetime comparison in vivo in the human RPE and may be a useful method for tracking diseases.

Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS.

UNASSIGNED: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.
UNASSIGNED: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.
UNASSIGNED: TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide 131I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and 131I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by 131I-labeled Atezolizumab and IgG in-vitro distribution.
UNASSIGNED: Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of 131I-labeled IgG was higher than that of 131I-labeled Atezolizumab at any time point.
UNASSIGNED: Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Carboxylesterase (CE), an enzyme widely present in organisms, is involved in various physiological and pathological processes. Changes in the levels of CEs in the liver may predict the presence of type 2 diabetes mellitus (T2DM). Here, a novel dicyanoisophorone (DCI)-based proximity-labeled far-red fluorescent probe DCI2F-Ac with endoplasmic reticulum targeting was proposed for real-time monitoring and imaging of the CEs activity. DCI2F-Ac featured very low cytotoxicity and biotoxicity and was highly selective and sensitive for CEs. Compared with traditional CEs probes, DCI2F-Ac was covalently anchored directly to CEs, thus effectively reducing the loss of in situ fluorescent signals due to diffusion. Through the \"on-off\" fluorescence signal readout, DCI2F-Ac was able to distinguish cell lines and screen for CEs inhibitors. In terms of endoplasmic reticulum (ER) stress, it was found that thapsigargin (Tg) induced upregulation of CEs levels but not tunicamycin (Tm), which was related to the calcium homeostasis of the ER. DCI2F-Ac could efficiently detect downregulated CEs in the livers of T2DM, and the therapeutic efficacy of metformin, acarbose, and a combination of these two drugs was assessed by tracking the fluctuation of CEs levels. The results showed that combining metformin and acarbose could restore CEs levels to near-normal levels with the best antidiabetic effect. Thus, the DCI2F-Ac probe provides a great opportunity to explore the untapped potential of CEs in liver metabolic disorders and drug efficacy assessment.

UNASSIGNED: To evaluate the relationships among morphology, fundus autofluorescence (FAF), and retinal sensitivity of photocoagulated lesions more than 1 year after panretinal photocoagulation in patients with proliferative diabetic retinopathy and good vision.
UNASSIGNED: This retrospective cohort study included patients with proliferative diabetic retinopathy who had undergone panretinal photocoagulation more than 1 year ago. The photocoagulated lesions were classified according to FAF levels: group A, no FAF; group B, diffuse FAF; group C, white-dotted centers with diffuse FAF; group D, white-dotted centers without FAF; and group E, controls. The main outcome measures were FAF, retinal sensitivity, and morphology of the photocoagulated lesions.
UNASSIGNED: The median sensitivity values and number of photocoagulated lesions in groups A (n = 37), B (n = 39), C (n = 4), D (n = 15), and E (n = 39) were 0 dB, 18.0 dB, 13.9 dB, 0.3 dB, and 21.5 dB, respectively. EZ lines were absent in 93.5%, 18.1%, 50%, 93.3%, and 0% of lesions in groups A, B, C, D, and E, respectively. The inner retinal layer was damaged in 45.2%, 3.0%, 50%, 73.3%, and 0% lesions in groups A, B, C, D, and E, respectively. Statistically significant between-group differences were observed in the retinal sensitivities of the photocoagulated lesions, presence of EZ lines, and damage to the inner retinal layer (p < 0.05).
UNASSIGNED: The photoreceptors in most photocoagulated lesions with diffuse FAF retain their morphology and function.
UNASSIGNED: Using fundus autofluorescence, the damage to photoreceptors after panretinal photocoagulation in patients with diabetes can be estimated in a noninvasive manner. This process can help in determining the need for additional panretinal photocoagulation.