2‐Propargyl alcohols are widely used in organic reactions. Their great success is rooted in the presence of multiple functional groups. This review will focus on six types of mechanisms: (i) ...2‐propargyl alcohols as carbocation precursors, (ii) alkynes as electrophiles, (iii) alcohols as nucleophiles, (iv) fracture via ketones or elimination into alkene intermediates, (v) oxidation into alkynyl‐ortho‐quinone methides or carbonyl intermediates, and (vi) ring expansions. Reactions involving alkanes, alkenes, alkynes, arenes, alcohols, amines, amides, ketones, CO2, hydrazine, iodobenzene, azides, carbenes, arylboronic acids, etc. will be discussed. We hope that this review will help to promote future research in this area.
Predicting the biological characteristics of hepatocellular carcinoma (HCC) is essential for personalized treatment. This study explored the role of ultrasound-based radiomics of peritumoral tissues ...for predicting HCC features, focusing on differentiation, cytokeratin 7 (CK7) and Ki67 expression, and p53 mutation status. A cohort of 153 patients with HCC underwent ultrasound examinations and radiomics features were extracted from peritumoral tissues. Subgroups were formed based on HCC characteristics. Predictive modeling was carried out using the XGBOOST algorithm in the differentiation subgroup, logistic regression in the CK7 and Ki67 expression subgroups, and support vector machine learning in the p53 mutation status subgroups. The predictive models demonstrated robust performance, with areas under the curves of 0.815 (0.683-0.948) in the differentiation subgroup, 0.922 (0.785-1) in the CK7 subgroup, 0.762 (0.618-0.906) in the Ki67 subgroup, and 0.849 (0.667-1) in the p53 mutation status subgroup. Confusion matrices and waterfall plots highlighted the good performance of the models. Comprehensive evaluation was carried out using SHapley Additive exPlanations plots, which revealed notable contributions from wavelet filter features. This study highlights the potential of ultrasound-based radiomics, specifically the importance of peritumoral tissue analysis, for predicting HCC characteristics. The results warrant further validation of peritumoral tissue radiomics in larger, multicenter studies.
Background
Hepatocellular cancer (HCC) is one of the most common tumors worldwide, and Ki-67 is highly important in the assessment of HCC. Our study aimed to evaluate the value of ultrasound ...radiomics based on intratumoral and peritumoral tissues in predicting Ki-67 expression levels in patients with HCC.
Methods
We conducted a retrospective analysis of ultrasonic and clinical data from 118 patients diagnosed with HCC through histopathological examination of surgical specimens in our hospital between September 2019 and January 2023. Radiomics features were extracted from ultrasound images of both intratumoral and peritumoral regions. To select the optimal features, we utilized the t-test and the least absolute shrinkage and selection operator (LASSO). We compared the area under the curve (AUC) values to determine the most effective modeling method. Subsequently, we developed four models: the intratumoral model, the peritumoral model, combined model #1, and combined model #2.
Results
Of the 118 patients, 64 were confirmed to have high Ki-67 expression while 54 were confirmed to have low Ki-67 expression. The AUC of the intratumoral model was 0.796 (0.649-0.942), and the AUC of the peritumoral model was 0.772 (0.619-0.926). Furthermore, combined model#1 yielded an AUC of 0.870 (0.751-0.989), and the AUC of combined model#2 was 0.762 (0.605-0.918). Among these models, combined model#1 showed the best performance in terms of AUC, accuracy, F1-score, and decision curve analysis (DCA).
Conclusion
We presented an ultrasound radiomics model that utilizes both intratumoral and peritumoral tissue information to accurately predict Ki-67 expression in HCC patients. We believe that incorporating both regions in a proper manner can enhance the diagnostic performance of the prediction model. Nevertheless, it is not sufficient to include both regions in the region of interest (ROI) without careful consideration.
Dynamic emissive materials in aqueous media have received much attention owing to their ease of preparation, tunable luminescence and environmental friendliness. However, hydrophobic fluorophores ...usually suffer from aggregation-caused quenching in water. In this work, we constructed an artificial light-harvesting system by using a non-covalent aggregation-induced emission dimer as antenna and energy donor. The dimer is quadruple hydrogen bonded from a ureidopyrimidinone derivative (
) containing a tetraphenylethylene group. The dispersed nano-assemblies based on the dimer in aqueous media were fabricated with the help of surfactant. By loading a hydrophobic acceptor molecule
into the nano-assemblies, man-made light-harvesting nanoparticles were fabricated, showing considerable energy transfer efficiency and a relatively high antenna effect. Additionally, the fluorescence color of the system can be gradually tuned by varying the content of the acceptors. This study provides a general way for the construction of an aqueous light-harvesting system based on a supramolecular dimer, which is important for potential application in luminescent materials.
In models of cancer cachexia, inhibiting type IIB activin receptors (ActRIIBs) reverse muscle wasting and prolongs survival, even with continued tumor growth. ActRIIB mediates signaling of numerous ...TGF‐β proteins; of these, we demonstrate that activins are the most potent negative regulators of muscle mass. To determine whether activin signaling in the absence of tumor‐derived factors induces cachexia, we used recombinant serotype 6 adeno‐associated virus (rAAV6) vectors to increase circulating activin A levels in C57BL/6 mice. While mice injected with control vector gained ~10% of their starting body mass (3.8±0.4 g) over 10 wk, mice injected with increasing doses of rAAV6:activin A exhibited weight loss in a dose‐dependent manner, to a maximum of –12.4% (–4.2±1.1 g). These reductions in body mass in rAAV6:activin‐injected mice correlated inversely with elevated serum activin A levels (7‐ to 24‐fold). Mechanistically, we show that activin A reduces muscle mass and function by stimulating the ActRIIB pathway, leading to deleterious consequences, including increased transcription of atrophy‐related ubiquitin ligases, decreased Akt/mTOR‐mediated protein synthesis, and a profibrotic response. Critically, we demonstrate that the muscle wasting and fibrosis that ensues in response to excessive activin levels is fully reversible. These findings highlight the therapeutic potential of targeting activins in cachexia.—Chen, J. L., Walton, K. L., Winbanks, C. E., Murphy, K. T., Thomson, R. E., Makanji, Y., Qian, H., Lynch, G. S., Harrison, C. A., Gregorevic, P. Elevated expression of activins promotes muscle wasting and cachexia. FASEB J. 28, 28–1711 (1723). www.fasebj.org
Abstract
Aims
The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models of diabetes, implicating ...protein O-GlcNAc modification in diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation of the two regulatory enzymes of this process on the cardiac phenotype, in the presence and absence of diabetes, utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery.
Methods and results
In human myocardium, total protein O-GlcNAc modification was elevated in diabetic relative to non-diabetic patients, and correlated with left ventricular (LV) dysfunction. The impact of rAAV6-delivered O-GlcNAc transferase (rAAV6-OGT, facilitating protein O-GlcNAcylation), O-GlcNAcase (rAAV6-OGA, facilitating de-O-GlcNAcylation), and empty vector (null) were determined in non-diabetic and diabetic mice. In non-diabetic mice, rAAV6-OGT was sufficient to impair LV diastolic function and induce maladaptive cardiac remodelling, including cardiac fibrosis and increased Myh-7 and Nppa pro-hypertrophic gene expression, recapitulating characteristics of diabetic cardiomyopathy. In contrast, rAAV6-OGA (but not rAAV6-OGT) rescued LV diastolic function and adverse cardiac remodelling in diabetic mice. Molecular insights implicated impaired cardiac PI3K(p110α)-Akt signalling as a potential contributing mechanism to the detrimental consequences of rAAV6-OGT in vivo. In contrast, rAAV6-OGA preserved PI3K(p110α)-Akt signalling in diabetic mouse myocardium in vivo and prevented high glucose-induced impairments in mitochondrial respiration in human cardiomyocytes in vitro.
Conclusion
Maladaptive protein O-GlcNAc modification is evident in human diabetic myocardium, and is a critical regulator of the diabetic heart phenotype. Selective targeting of cardiac protein O-GlcNAcylation to restore physiological O-GlcNAc balance may represent a novel therapeutic approach for diabetes-induced heart failure.
Graphical Abstract
Administration of cardiac targeted rAAV-OGT to the non-diabetic myocardium induced cardiac fibrosis, increased hypertrophic gene expression and reduced cardiac function, mimicking the diabetic heart. In contrast, administration of rAAV-OGA to the diabetic heart limits cardiac remodelling and dysfunction associated with diabetic cardiomyopathy. O-GlcNAcylation of the PI3K-Akt axis has been attributed to the cardiac pathological effects, while the opposite (de-GlcNAcylation) associated with cardioprotective.
Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) ...signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin-dependent process, whereas increased BMP-Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.
The uncertainty and destructiveness of major emergencies have resulted in China attaching unprecedented importance to emergency management. Ineffective response to emergencies also exposes the ...shortage of emergency management personnel and professionals, highlighting the necessity and urgency of emergency science education. Based on the actual needs of the state and society for emergency disciplines, this paper analyzes the logical possibilities of the emergency science and engineering discipline system design and gives a design framework. The study also puts forth measures to support implementation, such as conducting interdisciplinary pilot research and exploring the school's tradition of emergency science education. Including emergency science and engineering disciplines in interdisciplinary disciplines is conducive to enhancing resource investment, condensing academic consensus, accurately cultivating emergency personnel, achieving emergency technology breakthroughs, and providing a reference for the development of emergency science education in China.
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