Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. ...The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility are rationally designed, exhibiting fluorescence emission in the second near‐infrared window (NIR‐II, 1000–1700 nm) and high PCE, which are related to the strong donor–acceptor (D–A) interaction and high reorganization energy Noteworthily, ICR‐Qu with stronger D–A interaction and a large‐sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR‐QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep‐tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α‐PD‐1, ICR‐QuNPs show huge potential to be a facile and efficient tool for photo‐immunotherapy. More importantly, this study not only reports an “all‐in‐one” polymethine‐based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications.
Polymethine dyes with second near‐infrared emission and photoacoustic imaging capability are synthesized by the electronic‐donor group regulation strategy, which demonstrates high photothermal conversion efficiency (PCE = 81.1%) as an antitumor stategy in vivo and in vitro under the multimodal imaging guidance; theoretical calculation reveals the structure regulation mechanism for the polymethine‐based phototheranostic agent to achieve an excellent PCE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Non‐invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed ...so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non‐ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q‐P‐ARh dye, developed by us for the first time, can stain lysosomes at ultra‐low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti‐interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments.
A series of brand‐new large Stokes shift and highly stable fluorescent dyes were constructed. In particular, the Q‐P‐ARh fluorescent dye as a near‐infrared emission lysosomal‐specific probe with ultra‐low concentration and ultra‐fast staining characteristics for the complete lipophagy process imaging is presented.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Adopting healthy lifestyles and staying mentally health are two cost-effective modifiable strategies that cancer survivors can implement in self-management. We aimed to evaluate ...the independent, mediation, interaction, and joint associations of combined lifestyle and mental health with mortality in cancer survivors.
Methods
We performed a cohort study including 3145 cancer survivors from National Health and Nutrition Examination Survey (2005–2018). A healthy lifestyle score was constructed based on post-diagnosis body mass index, physical activity, diet, smoking, and drinking. Post-diagnosis mental health was assessed by Patient Health Questionnaire (PHQ-9). Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and non-cancer mortality were computed using Cox proportional hazards regression models.
Results
After 20,900 person-years of follow-up (median, 6.3 years), cancer survivors with higher lifestyle score had decreased mortality, independent of mental health. Compared to participants with lower lifestyle score (0–1), HRs (95% CIs) for all-cause and non-cancer mortality among those with higher lifestyle score (3–5) were 0.68 (0.52–0.89) and 0.69 (0.56–0.85), respectively. 6.2–10.3% of the associations were mediated by mental health. Similar trends were observed among participants categorized by mental health, those with better mental health had lower mortality, independent of lifestyle. Participants with better mental health benefited more from adopting healthy lifestyles, and vice versa. Combinations of higher healthy lifestyle score and better mental health were associated with significant decreased mortality, the lowest mortality was seen in participants with highest healthy lifestyle score and concurrently with best mental health.
Conclusions
For the first time, in this cohort study with a nationally representative sample of US cancer survivors, we comprehensively explored the complex associations of lifestyle, mental health, and mortality. Evidence derived from this study may give much confidence to cancer survivors and healthcare providers that, changing one’s lifestyle and/or staying mentally healthy after cancer diagnosis can improve survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Precise qualitative and quantitative analysis of phospholipid molecular species.•258 phospholipid molecular species were characterized in 486 human milk samples.•Dynamic changes of classes and sub ...classes of phospholipid over time were analyzed.•Critical change of phospholipid profile between lactation periods were analyzed.
Phospholipids are critical for milk digestion and infant development. But the profile of phospholipid molecular species in human milk and its dynamic changes during the lactation period have never been reported. The present study elucidated precise qualitative and quantitative analysis of 258 phospholipid molecular species in 486 human milk samples. Phosphatidylcholine is the most abundant class, followed by phosphatidylserine, phosphatidylethanolamine and sphingomyelin as the second abundant class in different lactation period. The plasmalogens declined along the lactation period, and the polyunsaturated-phospholipids decreased after 10–15 days. The decrease of phosphatidylcholines and phosphatidylglycerols, and the increase of lysophosphatidylethanolamines and lysophosphatidylcholines are critical changes from 0 to 5 days to 10–15 days; increase of phosphatidylinositols, phosphatidylserines, lysophosphatidylethanolamines and lysophosphatidylcholines is the key changes from 10–15 days to 40–45 days; the decrease of most phospholipid molecular species is the characteristic change from 40–45 days to 200–240 days; and the phospholipid profile achieved stability after 200 days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Organic molecules with second near‐infrared (NIR‐II, 1000–1700 nm) emission have significant advantages over NIR‐I (600–900 nm) dyes, and have been widely used as phototheranostic agents (PTAs) and ...fluorescent probes. However, the two biggest challenges for such reagents are improving photothermal conversion efficiency (PCE), and simplifying tedious synthetic procedures. Herein, different from the traditional NIR skeleton, for the first time, it develops two novel dibenzofulvene‐based NIR‐II emission PTAs via D‐π‐A concept with high PCEs through two simple synthetic steps. The increased intramolecular charge transfer effect and extended π‐conjugation effectively red‐shift their emissions to the NIR‐II region. In addition, the introduction of molecular rotors/vibrators and the formation of π–π stacking prompt the two PTAs to exhibit high PCEs. Notably, FE‐IDMN nanoparticles (FE‐IDMN NPs) achieve an exciting PCE of 82.6%, higher than most reported photothermal agents with NIR‐II emission. FE‐IDMN NPs also possess good colloidal, pH, and photothermal stabilities, as well as excellent photoacoustic response, which is further successfully applied for NIR‐II fluorescence/photoacoustic/photothermal imaging‐guided photothermal therapy. This work provides a simple strategy for constructing new D‐π‐A PTAs with low molecular weight, NIR‐II emission, and high PCE for cancer therapy.
A novel low‐molecular‐weight dibenzofulvene‐based D‐π‐A phototheranostic agent (PTA) with NIR‐II emission and high PCE is developed by the strategies of enhancing D‐A strength, introducing molecular rotors/vibrators, and facilitating intermolecular π–π stacking. The PTA is successfully applied in the multi‐modal imaging (NIR‐II fluorescence/photoacoustic/photothermal imaging)‐guided photothermal therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of ...hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer‐specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22–2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36–3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89–1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99–2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.
What's new?
Copper and zinc are essential micronutrients whose imbalance may be involved in development and progression of cancer. Currently, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) however remains unclear. The authors examine for the first time whether serum levels of copper, zinc, and their ratios are associated with survival in a large prospective cohort of newly diagnosed patients. The findings suggest that higher copper levels and copper/zinc ratios are associated with worse survival, but serum zinc levels are not associated with HCC survival. The results may have important implications for the prognosis of HCC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel
-amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of ...Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.
Background and Aims
Free and bioavailable 25‐hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to ...hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival.
Approach and Results
We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum‐free 25OHD levels were measured using a two‐step enzyme‐linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer–specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow‐up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C‐reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable‐adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS.
Conclusions
Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population‐based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
High‐performance fluorescent probes stand as indispensable tools in fluorescence‐guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of ...healthy tissue. Herein, machine‐learning‐assisted strategy to investigate the current available xanthene dyes is first proposed, and a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with the desired pH responsivity is constructed. Two novel Si─rhodamine derivatives are successfully achieved and the cathepsin/pH sequentially activated probe Si─rhodamine─cathepsin‐pH (SiR─CTS‐pH) is constructed. The results reveal that SiR─CTS‐pH exhibits higher signal‐to‐noise ratio of fluorescence imaging, compared to single pH or cathepsin‐activated probe. Moreover, SiR─CTS‐pH shows strong differentiation abilities for tumor cells and tissues and accurately discriminates the complex hepatocellular carcinoma tissues from normal ones, indicating its significant application potential in clinical practice. Therefore, the continuous development of xanthene dyes and the rational design of superior fluorescent molecules through machine‐learning‐assisted model broaden the path and provide more advanced methods to researchers.
The development of machine learning has dramatically revolutionized the process of material discovery. Here, the desired xanthene dyes are rational designed through machine learning and dual‐locked probe for precise imaging of complex hepatocellular carcinoma is constructed. These results not only affirm the validity of the model but also guide the design of novel probes with practical applications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background & Aims
Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 ...levels and HCC survival in a large prospective cohort.
Methods
825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer‐specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P‐trend = .014) and 1.48 (95% CI: 1.12, 1.97; P‐trend = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0 kg/m2, except for that stronger associations were observed in patients co‐occurred more than three metabolic disorder diseases (P‐interaction = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P‐trend = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P‐trend = .195) for LCSS.
Conclusions
Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism‐related prognostic biomarker for HCC.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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