Phototheranostics represents a promising direction for modern precision medicine, which has recently attracted great research interest from multidisciplinary research areas. Organic optical agents ...including small molecular fluorophores, semiconducting/conjugated polymers, aggregation-induced emission luminogens,
etc.
with tuneable photophysical properties, high biosafety and biocompatibility, facile processability and ease of functionalization have delivered encouraging performance in disease phototheranostics. This review summarizes the recent progress of organic phototheranostic agents with an emphasis on the main strategies to manipulate the three excitation energy dissipation pathways, namely, radiative decay, thermal deactivation, and intersystem crossing, with the assistance of a Jablonski diagram, which particularly showcases how the Jablonski diagram has been guiding the design of organic agents from molecule to aggregate levels to promote the disease phototheranostic outcomes. Molecular design and nanoengineering strategies to modulate photophysical processes of organic optical agents to convert the absorbed photons into fluorescent/phosphorescent/photoacoustic signals and/or photodynamic/photothermal curing effects for improved disease phototheranostics are elaborated. Noteworthily, adaptive phototheranostics with activatable and transformable functions on demand, and regulation of excitation such as chemiexcitation to promote the phototheranostic efficacies are also included. A brief summary with the discussion of current challenges and future perspectives in this research field is further presented.
This review summarizes how Jablonski diagrams guide the design of advanced organic optical agents and improvement of disease phototheranostic efficacies.
J-aggregation is an efficient strategy for the development of fluorescent imaging agents in the second near-infrared window. However, the design of the second near-infrared fluorescent J-aggregates ...is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso-2.2paracyclophanyl-3,5-bis-N,N-dimethylaminostyrl BODIPY (PCP-BDP2) as an example of BODIPY dye with J-aggregation induced the second near-infrared fluorescence. PCP-BDP2 shows an emission maximum at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY play key roles in the J-aggregation behavior and photophysical properties tuning. Notably, PCP-BDP2 J-aggregates can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study demonstrates BODIPY dye as an alternate J-aggregation platform for developing the second near-infrared imaging agents.
The gold standard for diagnosing sleep disorders is polysomnography, which generates extensive data about biophysical changes occurring during sleep. We developed the National Sleep Research Resource ...(NSRR), a comprehensive system for sharing sleep data. The NSRR embodies elements of a data commons aimed at accelerating research to address critical questions about the impact of sleep disorders on important health outcomes.
We used a metadata-guided approach, with a set of common sleep-specific terms enforcing uniform semantic interpretation of data elements across three main components: (1) annotated datasets; (2) user interfaces for accessing data; and (3) computational tools for the analysis of polysomnography recordings. We incorporated the process for managing dataset-specific data use agreements, evidence of Institutional Review Board review, and the corresponding access control in the NSRR web portal. The metadata-guided approach facilitates structural and semantic interoperability, ultimately leading to enhanced data reusability and scientific rigor.
The authors curated and deposited retrospective data from 10 large, NIH-funded sleep cohort studies, including several from the Trans-Omics for Precision Medicine (TOPMed) program, into the NSRR. The NSRR currently contains data on 26 808 subjects and 31 166 signal files in European Data Format. Launched in April 2014, over 3000 registered users have downloaded over 130 terabytes of data.
The NSRR offers a use case and an example for creating a full-fledged data commons. It provides a single point of access to analysis-ready physiological signals from polysomnography obtained from multiple sources, and a wide variety of clinical data to facilitate sleep research.
Persistent luminescence without excitation light and tissue autofluorescence interference holds great promise for biological applications, but is limited by available materials with long‐wavelength ...emission and excellent clinical potential. Here, we report that porphyrin derivatives can emit near‐infrared persistent luminescence over 60 min after cessation of excitation light or on interaction with peroxynitrite. A plausible mechanism of the successive oxidation of vinylene bonds was demonstrated. A supramolecular probe with a β‐sheet structure was constructed to enhance the tumor targeting ability and the photoacoustic and persistent luminescence signals. Such probes featuring light‐triggered function transformation from photoacoustic imaging to persistent luminescence imaging permit advanced image‐guided cancer surgery. Furthermore, peroxynitrite‐activated persistent luminescence of the supramolecular probe also enables rapid and precise screening of immunogenic cell death drugs.
Porphyrin derivatives that can emit near‐infrared persistent luminescence (PL) over 60 min are reported and a mechanism for the phenomenon is proposed. The derivatives are used to synthesize supramolecular probes with peroxynitrite‐activated PL and light‐triggered imaging‐modality transformation characteristics that permit improved biological uses.
Development of the powerful building block is of great significance to construct materials with advanced properties. Herein, for the first time, a triazole‐based luminescent core with balanced twist ...and conjugation is reported, which is explored to construct a D‐A near‐infrared (NIR) aggregation‐induced emission luminogens (TPT‐DCM) with high molar extinction coefficient, good brightness and excellent reactive oxygen species generation rate. These features enable it to function as a nanoprobe with ultralong NIR afterglow luminescence (up to 20 days) and ultrahigh tumor‐to‐liver signal ratio (up to 187) for in vivo deep‐tissue afterglow imaging (with depth reaching 1.6 cm), in combination with chemiluminescence resonance energy transfer aided by active Schaap's dioxetane. Moreover, thanks to the excellent properties of the nanoprobe, the afterglow imaging‐guided surgery navigation can be successfully conduced to remove the tumors especially with tiny size of < 1 mm. This is particularly useful to eliminate tumor residuals and prevent the cancer recurrence after surgery.
Robust trizole‐based luminescent core with balanced twist and conjugation is reported to construct near‐infrared (NIR) aggregation‐induced emission luminogens (TPT‐DCM) and ultralong NIR afterglow nanoprobe, which shows great potential for high‐contrast tumor imaging and afterglow imaging‐guided surgery navigation.
Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL‐17A in lung injury, while its contribution to ...PM2.5‐induced lung injury remains largely unknown. Here, we probed into the possible role of IL‐17A in mouse models of PM2.5‐induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway‐, autophagy‐ and PI3K/Akt/mTOR signalling pathway‐related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL‐17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up‐regulating IL‐17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL‐17A impaired the energy metabolism of airway epithelial cells in the PM2.5‐induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL‐17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.
Automatic identification of sleep stage is an important step in a sleep study. In this paper, we propose a hybrid automatic sleep stage scoring approach, named HyCLASSS, based on single channel ...electroencephalogram (EEG). HyCLASSS, for the first time, leverages both signal and stage transition features of human sleep for automatic identification of sleep stages. HyCLASSS consists of two parts: A random forest classifier and correction rules. Random forest classifier is trained using 30 EEG signal features, including temporal, frequency, and nonlinear features. The correction rules are constructed based on stage transition feature, importing the continuity property of sleep, and characteristic of sleep stage transition. Compared with the gold standard of manual scoring using Rechtschaffen and Kales criterion, the overall accuracy and kappa coefficient applied on 198 subjects has reached 85.95% and 0.8046 in our experiment, respectively. The performance of HyCLASS compared favorably to previous work, and it could be integrated with sleep evaluation or sleep diagnosis system in the future.
There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted ...an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio RR 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ischemia/reperfusion (IR) injury contributes to disability and mortality worldwide. Due to the complicated mechanisms and lack of proper therapeutic targets, few interventions are available that ...specifically target the pathogenesis of IR injury. Regulated cell death (RCD) of endothelial and parenchymal cells is recognized as the promising intervening target. Recent advances in IR injury suggest that small molecules exhibit beneficial effects on various RCD against IR injury, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, and parthanatos. Here, we describe the mechanisms behind these novel promising therapeutic targets and explain the machinery powering the small molecules. These small molecules exert protection by targeting endothelial or parenchymal cells to alleviate IR injury. Therapies of the ideal combination of small molecules targeting multiple cell types have shown potent synergetic therapeutic effects, laying the foundation for novel strategies to attenuate IR injury.
Programmed cell death ligand 1 (PD‐L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL‐6) in T cell lymphoma and ovarian cancer. The ...purpose of this study is to investigate the expression of IL‐6 and PD‐L1 in thyroid cancer, and whether IL‐6 regulates PD‐L1 expression. As a result, IL‐6 and PD‐L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL‐6 expression (P < .05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL‐6 expression were identified as the independent predictors of PD‐L1 expression (P < .05). The invasiveness of thyroid cancer was significantly enhanced after IL‐6 treatment or PD‐L1 overexpression. PD‐L1 positive rate correlated with IL‐6 expression in cancer tissues (P < .001), and after IL‐6 treatment, the PD‐L1 expression in TPC‐1 and BCPAP significantly increased. The mitogen‐activated protein kinase pathway (MAPK) and the Janus‐activated kinase (JAK)–signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL‐6, and the IL‐6–induced PD‐L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c‐Jun and stat3 suppressed the expression of PD‐L1 induced by IL‐6, and these two factors could bind to PD‐L1 gene promoter directly and promote its transcription. It is concluded that IL‐6 and PD‐L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. IL‐6 upregulates PD‐L1 expression through the MAPK and JAK‐STAT3 signaling pathways, which function via transcription factors c‐Jun and stat3.
IL‐6 and PD‐L1 are highly expressed in thyroid cancer and correlate with disease aggressiveness. IL‐6 activates the MAPK and JAK‐STAT3 signaling pathways in thyroid cancer. In addition, IL‐6 promotes PD‐L1 transcription through the MAPK and JAK‐STAT3 signaling pathways, which function via transcription factors c‐Jun and stat3.
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