Excited‐state intramolecular proton transfer (ESIPT) process brings about ultrafast keto‐enol tautomerism, which simultaneously induces the unique four‐leveled energy state cycle and concomitant ...multi‐emissions. Such transformation is easily affected by the environmental conditions, leading to intricate spectral responses. In contrast with the widely reported researches that inclined to the solution systems dissolved with ESIPT molecules, ESIPT materials including small organic molecules, metal‐organic materials, covalent‐organic frameworks, and so on, which can be formed in solid state are emerging in recent years, bringing more scientific information and novel applications for the family of ESIPT materials. In this short review, the progress for the different types of these materials will be introduced, especially their optical sensing performances and mechanisms, like responses to external physical stimulations (pressure, temperature, light), solvent polarities, pH, ions, and small molecule compounds. And the potential photophysical and photochemical applications will also be surveyed.
In this review, a summary introduction of ESIPT (excited state intramolecular proton transfer) materials in the solid state including small organic molecules, metal‐organic frameworks, and covalent‐organic frameworks is given. The four‐leveled energy state cycle based keto‐enol emissions of these materials respond to temperature, pressure, solvent, ions, light, and so on, and can be applied widely in optical sensing fields.
Background
Diabetic retinopathy (DR) is a common complication of diabetes mellitus that poses a threat to adults. MicroRNAs (miRNAs) play a key role in DR progression. However, the role and mechanism ...of miR‐192‐5p in DR remain unclear. We aimed to investigate the effect of miR‐192‐5p on cell proliferation, migration and angiogenesis in DR.
Methods
Expression of miR‐192‐5p, ELAV‐like RNA binding protein 1 (ELAVL1) and phosphoinositide 3‐kinase delta (PI3Kδ) in human retinal fibrovascular membrane (FVM) samples and human retinal microvascular endothelial cells (HRMECs) was assessed using RT‐qPCR. ELAVL1 and PI3Kδ protein levels were evaluated by Western blot. RIP and dual luciferase reporter assays were performed to confirm the miR‐192‐5p/ELAVL1/PI3Kδ regulatory networks. Cell proliferation, migration and angiogenesis were assessed by CCK8, transwell and tube formation assays.
Results
MiR‐192‐5p was decreased in FVM samples from DR patients and high glucose (HG)‐treated HRMECs. Functionally, overexpressed miR‐192‐5p inhibited cell proliferation, migration and angiogenesis in HG‐treated HRMECs. Mechanically, miR‐192‐5p directly targeted ELAVL1 and decreased its expression. We further verified that ELAVL1 bound to PI3Kδ and maintained PI3Kδ mRNA stability. Rescue analysis demonstrated that the suppressive effects of HG‐treated HRMECs caused by miR‐192‐5p up‐regulation were overturned by overexpressed ELAVL1 or PI3Kδ.
Conclusion
MiR‐192‐5p attenuates DR progression by targeting ELAVL1 and reducing PI3Kδ expression, suggesting a biomarker for the treatment of DR.
Composition and diversity in gut microbiota are impacted by a wide variety of factors. The similarity of gut microbiota in related or sympatric species has been gaining recent traction. Here, 16S ...rRNA gene sequencing technology was employed to study the gut microbiota of three sympatric frog species, namely Odorrana tormota, O. graminea, and Amolops wuyiensis. In these three frog species, the most abundant phylum was Proteobacteria, followed by Bacteroidetes, Verrucomicrobia, and Firmicutes. The most abundant family was Burkholderiaceae in three species. The most dominant genera were Burkholderia, Caballeronia, and Paraburkholderia with the highest relative abundance in O. tormota, O. graminea, and A. wuyiensis, respectively. No differences were observed in alpha diversity indexes among the three frog species. However, bacterial similarity of gut microbiota was significantly different between O. tormota and A. wuyiensis and between O. graminea and A. wuyiensis. Metabolism‐related gene function was predominantly enriched in the gut microbiota of the three evaluated frog species. From these findings, that the relative abundance of the gut microbiota and predicted gene functions differed in three species, we conclude that there were significant differences in the gut microbiota of the three species. Similar alpha diversity and interspecific bacterial similarity in the gut might be related to bacterial transmission among the three Anura frogs evaluated in this study.
These three Anura frogs are commonly observed on rocks near streams. These species are distributed along mountain streams and congregate in large numbers during the breeding reason in mountain streams. This will provide a good model for the study on the gut microbial differences in sympatric frogs.
To investigate the effects of age at diagnosis on metastatic breast cancer and patients' prognosis, we collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. We ...finally identified 4932 eligible metastatic breast cancer patients diagnosed between 2010-2013, including 850 younger patients (<50 years), 2,540 middle-aged patients (50-69 years) and 1,542 elder patients (>69 years). The results revealed that in stage IV patients, elder patients were more likely to have lung metastasis (P < 0.001) and less likely to have only distant lymphatic spread (P = 0.004). Higher proportion of younger (34.9%) and middle-aged (36.2%) patients had multiple metastatic sites than elder patients (28.3%) (P < 0.001). In survival analysis, younger patients presented the best prognosis, while elder patients had the worst both in overall survival (χ
= 121.9, P < 0.001) and breast cancer-specific survival (χ
= 69.8, P < 0.001). Age at diagnosis was an independent prognostic factor for metastatic breast cancer patients. Moreover, patients with bone metastasis only had superior survival compared to other metastatic patients (P < 0.001). Brain metastasis only group and multiple sites metastasis group had the poorest prognosis (P < 0.05). We hope the results will provide insights into a better understanding of distant metastatic breast cancer.
Bovine serum albumin (BSA) is chosen as the nucleation templates to synthesize Pt-based peroxidase nanomimetics with the average diameter of 2.0nm. The efficient Pt nanozymes consist of 57% Pt0 and ...43% Pt2+, which possess highly peroxidase-like activity with the Km values of 0.119mM and 41.8mM toward 3,3′,5,5′-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), respectively. Interestingly, Hg2+ is able to down-regulate the enzymatic activity of Pt nanoparticles, mainly through the interactions between Hg2+ and Pt0. It is the first report to explore a colorimetric Hg2+ sensing system on the basis of peroxidase mimicking activities of Pt nanoparticles. One of our most intriguing results is that BSA-stabilized Pt nanozymes demonstrate the ability to sense Hg2+ ions in aqueous solution without significant interference from other metal ions. The Hg2+ detection limit of 7.2nM is achieved with a linear response range of 0–120nM, and the developed sensing system is potentially applicable for quantitative determination of Hg2+ in drinking water.
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•BSA stabilizes Pt nanoparticles of 2nm.•Pt nanoparticles possess intrinsic peroxidase-like activity.•Hg2+ ions down-regulate the enzymatic activity of Pt nanoparticles.•Pt nanozyme can sense Hg2+ ions in aqueous solution and drinking water.•The detection limit of 7.2nM is achieved without significant interference.
RATIONALE:Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with ...advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown.
OBJECTIVE:In this study, we investigated the role of Sirtuin 1 (SIRT1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation.
METHODS AND RESULTS:The expression and activity of SIRT1 were significantly decreased in human AAA samples. SIRT1 in vascular smooth muscle cells (VSMCs) was remarkably downregulated in the suprarenal aortas of aged mice, in which AAAs induced by Ang II infusion were significantly elevated. Moreover, VSMC-specific knockout of SIRT1 accelerated Ang II-induced formation and rupture of AAAs and AAA-related pathological changes, whereas VSMC-specific overexpression of SIRT1 suppressed Ang II-induced AAA formation and progression in Apoe mice. Furthermore, the inhibitory effect of SIRT1 on AAA formation was also proved in a calcium chloride (CaCl2)–induced AAA model. Mechanistically, the reduction of SIRT1 was shown to increase vascular cell senescence and upregulate p21 expression as well as enhance vascular inflammation. Notably, inhibition of p21-dependent vascular cell senescence by SIRT1 blocked Ang II-induced NF-κB binding on the promoter of monocyte chemoattractant protein-1 (MCP-1/CCL2) and inhibited its expression.
CONCLUSION:These findings provide evidence that SIRT1 reduction links vascular senescence and inflammation to AAAs, and that SIRT1 in VSMCs provides a therapeutic target for the prevention of AAA formation.
It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease ...(COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2 weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3 days or 1 month.
,
, and
mice and neutralising antibodies against active elastin fragments were used for mechanistic investigations. Human GVAPGVGVAPGV/HLA-A*02:01 tetramer was synthesised to assess the presence of elastin-specific T cells in patients with COPD.We observed that 2 weeks of cigarette smoke exposure induced an elastin-specific T cell response that led to neutrophilic airway inflammation and mucus hyperproduction following elastin recall challenge. Repeated elastin challenge for 1 month resulted in airway remodelling, lung function decline and airspace enlargement. Elastin-specific T cell recall responses were dose dependent and memory lasted for over 6 months. Adoptive T cell transfer and studies in T cells deficient
mice conclusively implicated T cells in these processes. Mechanistically, cigarette smoke exposure-induced elastin-specific T cell responses were matrix metalloproteinase (MMP)12-dependent, while the ensuing immune inflammatory processes were interleukin 17A-driven. Anti-elastin antibodies and T cells specific for elastin peptides were increased in patients with COPD.These data demonstrate that MMP12-generated elastin fragments serve as a self-antigen and drive the cigarette smoke-induced autoimmune processes in mice that result in a bronchitis-like phenotype and airspace enlargement. The study provides proof of concept of cigarette smoke-induced autoimmune processes and may serve as a novel mouse model of COPD.
Opportunistic maintenance (OM), which shows its superiority on complex multi-component systems by integrating the maintenance activities of multiple components to reduce the maintenance cost, has ...been widely studied over the past decade. To our knowledge, most of the existing OM works are developed based on fixed maintenance thresholds without fully utilizing the health state of the multi-component system. This article presents an OM optimization problem of multi-component systems with load sharing, solved by a modified proximal policy optimization approach based on deep reinforcement learning algorithm. The load sharing effect is reflected in the hazard rate function, which further changes the failure probability of the components. Meanwhile, the health states can be recovered by executing imperfect maintenance and corrective maintenance. The optimization problem is formulated as an infinite-horizon MDP with mixed discrete and continuous state and action space to maximize the total discounted reward, taking into account the system reliability and the maintenance cost. The difficulty caused by the mixed action space is solved by designing a parameterized action space structure and multi-task reinforcement learning framework. The effectiveness of the proposed algorithm is tested on a four-component system and a real-world scenario configured with the high-pressure feedwater heater system in the nuclear power plant. The results show that the performance of the algorithm is stable when facing large-scale problems. The algorithm proposed in this study also contributes to the imperfect maintenance optimization with state-of-the-art optimization techniques.
Objective
It has been reported that metabolic syndrome (MetS) has been associated with hyperuricemia. However, current findings have been inconclusive regarding the direction of this association. The ...objective of this study was to clarify the possible directional relationship between hyperuricemia and MetS.
Design
This study used two waves of data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015 (
N
= 6,253, aged ≥40 years). Logistic regression and cross-lagged panel design were performed to evaluate the bidirectional association between uric acid with MetS. MetS score is defined as the number of MetS components present.
Results
New-onset hyperuricemia and MetS were observed in a four-year follow-up study among 719 and 625 participants, respectively. A positive association was observed in the adjusted logistical regression model between baseline MetS score and new-onset hyperuricemia (
P
for trend <0.001), and also between baseline serum uric acid (SUA) and new-onset MetS (
P
for trend <0.001). Cross-lagged panel analysis indicated MetS score positively and prospectively predicted SUA, but not vice versa. After stratification by sex, we observed a strong, bidirectional relationship between MetS score and SUA indicating that diagnosis in one illness increased the risk of the other, both men and women. Moreover, this study also found that systolic blood pressure (
P
< 0.001) and triglycerides (
P
< 0.001) had a bidirectional relationship with SUA.
Conclusions
The results of this study indicated a bidirectional relationship between MetS and hyperuricemia.
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