Role of peritumoral tissue analysis in predicting characteristics of hepatocellular carcinoma using ultrasound-based radiomics.

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.

A radiomics model based on transrectal ultrasound for predicting prostate cancer.

AIM: Prostate cancer (PCa) is one of the most common neoplasms in men. However, the value of ultrasound-based radiomics for diagnosing PCa remains uncertain. MATERIAL AND METHODS: We retrospectively analyzed ultrasonic and clinical data from 373 patients. Patients were divided into two groups according to the pathological results. Radiomics features wereextracted from TRUS, and we screened the optimal features to construct radiomics models. Relationships between clinical characteristics and prostate lesions were identified by univariate and multivariate logistic regression analysis. Finally, a clinical-radiomics model was developed, and then visualized in the form of a nomogram. RESULTS: Of the 373 patients, 178 had benign disease and 195 had malignant disease. The support vector machine (SVM) classification model showed the best performance, while the diagnostic performance of the clinical model was poorer than that of the radiomics model (p<0.05) or the combined (clinical-radiomics) model (p<0.05). In general, the combined model demonstrated the highest AUC and proved to be more advantageous. CONCLUSION: The prediction model we constructed based on TRUS predicted PCa preoperatively with high efficiency. In addition, combining radiomics with clinical factors improved diagnostic accuracy.

Intratumoral and peritumoral radiomics model based on abdominal ultrasound for predicting Ki-67 expression in patients with hepatocellular cancer.

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.

Aryl boronic acid-controlled divergent ring-contraction and ring-opening/isomerization reaction of tert-cyclobutanols enabled by nickel catalysis.

In this work, we wish to present a nickel-catalyzed divergent ring-contraction and ring-opening/isomerization reaction of tert-cyclobutanols. The key to control these two different reaction pathways is to choose appropriate boronic acid, where the use of phenylboronic acid and pyrimidin-5-ylboronic acid enables a ring-contraction and ring-opening reaction/isomerization, respectively. Both cyclopropyl aryl methanones and 1-aryl butan-1-ones could be selectively obtained.

The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

Nickel-catalyzed divergent formylation and carboxylation of aryl halides with isocyanides.

Herein, we describe a nickel-catalyzed divergent formylation and carboxylation reaction of aryl halides with isocyanides. A rich array of aromatic aldehydes and carboxylic acids can be, respectively, accessed in moderate to good yields. Some sensitive functional groups such as hydroxyl, iodine, cyano, and indolyl are fairly tolerant of nickel catalysis. In the carboxylation reactions, the combination of isocyanide and H2O is first employed as a promising carbonyl surrogate instead of gaseous CO and CO2.

Non-Covalent Dimer as Donor Chromophore for Constructing Artificial Light-Harvesting System in Water.

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 (M) 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 DBT 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.

Influencing Factors and Improvement Path of Academic Engagement among College Students in the Context of Epidemic Prevention and Control.

OBJECTIVE: The implementation of online teaching in the context of epidemic prevention and control has had an impact on the learning engagement of college students to some extent. This study aims to investigate the mechanisms that influence perceived social support and health behaviors on learning engagement, so as to make college students more focused on their studies by improving their physical and mental health as well as their ability to perceive social support. METHODS: A total of 538 college students from Henan Province, China, were studied using the Perceived Social Support Scale, Health Behavior Scale and Learning Engagement Scale, and the data were analyzed by IBM SPSS Amos 26.0 software (IBM SPSS Inc., Chicago, IL, USA). RESULTS: (1) The level of health behavior among college students was positively correlated with perceived social support ability (ß = 0.289, p < 0.001); both perceived social support and health behaviors predicted college students' learning engagement significantly (ß = 0.200, p < 0.01; ß = 0.406, p < 0.001). (2) College students' perceived social support partially mediated the relationship between health behaviors and learning engagement. CONCLUSION: One of the main ways to improve college students' learning engagement is to improve their health behavior and perceived social support. This study contributes to a better understanding of the relationships between health behaviors and learning engagement, as well as to the development of interventions to improve learning engagement among college students.

Skeletal muscle metastasis from extrahepatic cholangiocarcinoma: A case report and literature review.

Background: Cholangiocarcinoma (CCA) is a type of malignant tumor that arises from the epithelium of the bile ducts. According to anatomical location, CCA can be classified as intrahepatic (ICC), perihilar (PCC), or extrahepatic (ECC). CCA can invade and metastasize to other tissues in various ways, but distal skeletal muscle metastasis (SMM) is extremely rare. There are several reports on SMM from ICC or PCC, but SMM from ECC has not yet been reported. Case presentation: A 71-year-old woman was diagnosed with ECC, for which she underwent pancreatoduodenectomy and partial hepatectomy. Nine months after surgery, she was re-admitted to the hospital complaining of a rapidly growing mass on her right thigh with progressive lower extremity edema. Magnetic resonance imaging of the right thigh showed two masses with iso-signal intensity on T1-weighted images and hyper-intensity on T2-weighted images compared with the surrounding muscles. Pathological examination of the fine-needle biopsy specimen revealed that it was similar to the previously detected ECC, and the diagnosis was metastasis of ECC. The patient was treated with opioid analgesics and died of systemic failure three months later. Conclusion: SMM should be considered during the follow-up period despite its low incidence, and perineural invasion may be an essential pathway of distant metastasis in CCA.

Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function.

Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise. One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca2+ handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.

An ultralow-acceptor-content supramolecular light-harvesting system for white-light emission.

White-light emission in donor-acceptor systems usually requires relatively high acceptor content and/or multiple acceptors to "neutralize" the primary color of donors. Herein, a cyanostilbene-bridged ditopic ureidopyrimidinone donor (CSU) was designed and synthesized, which can self-assemble into dispersed nanoparticles in water. Fascinatingly, efficient white-light emission can be realized by co-assembling 0.1% DBT into the nanoparticles through a light-harvesting strategy. This new system is further demonstrated for use in white-light encryption materials.

Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart.

AIMS: The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, ß-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.

A male congenital pelvic arteriovenous malformation diagnosed by abdominal ultrasound: A case report and literature review.

Congenital pelvic arteriovenous malformation (AVM) is a rare vascular abnormality whereby arteries and veins are directly connected with malformed vascular plexus. Owing to its low incidence and nonspecific symptoms, the ultrasonographic characteristics of congenital pelvic AVM in males have been infrequently studied. A 30-year-old man visited our hospital complaining of progressive pain in the right lower abdomen and lumbar area since 2 months previously. Abdominal ultrasound (US) was performed at the initial examination and pelvic AVM was diagnosed, which was then confirmed by computed tomographic angiography. After right internal iliac artery embolization, the patient recovered uneventfully and remained asymptomatic during the 12-month follow-up period. Congenital pelvic AVM should thus be included in the differential diagnosis of pelvic cystic masses in males despite its low incidence, with US also being of great diagnostic value. We describe the ultrasonic features of AVM in detail and hope that this study may contribute to the ultrasonic diagnosis of congenital pelvic AVM in males.

Bone Morphogenetic Protein 7 Gene Delivery Improves Cardiac Structure and Function in a Murine Model of Diabetic Cardiomyopathy.

Diabetes is a major contributor to the increasing burden of heart failure prevalence globally, at least in part due to a disease process termed diabetic cardiomyopathy. Diabetic cardiomyopathy is characterised by cardiac structural changes that are caused by chronic exposure to the diabetic milieu. These structural changes are a major cause of left ventricular (LV) wall stiffness and the development of LV dysfunction. In the current study, we investigated the therapeutic potential of a cardiac-targeted bone morphogenetic protein 7 (BMP7) gene therapy, administered once diastolic dysfunction was present, mimicking the timeframe in which clinical management of the cardiomyopathy would likely be desired. Following 18 weeks of untreated diabetes, mice were administered with a single tail-vein injection of recombinant adeno-associated viral vector (AAV), containing the BMP7 gene, or null vector. Our data demonstrated, after 8 weeks of treatment, that rAAV6-BMP7 treatment exerted beneficial effects on LV functional and structural changes. Importantly, diabetes-induced LV dysfunction was significantly attenuated by a single administration of rAAV6-BMP7. This was associated with a reduction in cardiac fibrosis, cardiomyocyte hypertrophy and cardiomyocyte apoptosis. In conclusion, BMP7 gene therapy limited pathological remodelling in the diabetic heart, conferring an improvement in cardiac function. These findings provide insight for the potential development of treatment strategies urgently needed to delay or reverse LV pathological remodelling in the diabetic heart.

Perturbed BMP signaling and denervation promote muscle wasting in cancer cachexia.

Most patients with advanced solid cancers exhibit features of cachexia, a debilitating syndrome characterized by progressive loss of skeletal muscle mass and strength. Because the underlying mechanisms of this multifactorial syndrome are incompletely defined, effective therapeutics have yet to be developed. Here, we show that diminished bone morphogenetic protein (BMP) signaling is observed early in the onset of skeletal muscle wasting associated with cancer cachexia in mouse models and in patients with cancer. Cancer-mediated factors including Activin A and IL-6 trigger the expression of the BMP inhibitor Noggin in muscle, which blocks the actions of BMPs on muscle fibers and motor nerves, subsequently causing disruption of the neuromuscular junction (NMJ), denervation, and muscle wasting. Increasing BMP signaling in the muscles of tumor-bearing mice by gene delivery or pharmacological means can prevent muscle wasting and preserve measures of NMJ function. The data identify perturbed BMP signaling and denervation of muscle fibers as important pathogenic mechanisms of muscle wasting associated with tumor growth. Collectively, these findings present interventions that promote BMP-mediated signaling as an attractive strategy to counteract the loss of functional musculature in patients with cancer.

Supramolecular polymer-directed light-harvesting system based on a stepwise energy transfer cascade.

The design and construction of an artificial light-harvesting system in water by mimicking the energy transfer cascade in natural photosynthesis are of significant importance. Herein, we report an efficient two-step sequential energy transfer system based on quadruple hydrogen-bonded supramolecular polymeric nanoparticles. By loading two types of hydrophobic dyes as energy acceptors, excitation energy from the supramolecular polymer could be funneled efficiently to the final acceptor through the relay acceptor. The system exhibits tunable multicolor emission from blue through yellow to red, as well as white light emission.

Integrated Glycoproteomics Identifies a Role of N-Glycosylation and Galectin-1 on Myogenesis and Muscle Development.

Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases, suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development, but our molecular understanding of the precise glycans, catalytic enzymes, and lectins involved remains only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown digalactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labeling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins, most notably the upregulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation, suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the upregulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.

Efficient artificial light-harvesting system constructed from supramolecular polymers with AIE property.

Supramolecular luminescent materials in water have attracted much interest due to their excellent tunability, multi-color emission, and environment-friendly behavior. However, hydrophobic chromophores are often affected by poor solubility and aggregation-caused quenching effects in aqueous media. Herein, we report a water-phase artificial light-harvesting system based on an AIE-type supramolecular polymer. Specifically, dispersed nanoparticles in water were prepared from an AIE chromophore-bridged ditopic ureidopyrimidinone (M) based supramolecular polymer with the assistance of surfactants. By co-assembling the hydrophobic chromophores NDI as energy acceptor into the nanocarriers, artificial light-harvesting systems (M-NDI) could be successfully constructed, exhibiting efficient energy transfer and high antenna effects. Furthermore, the spectral emission of the system could be continuously tuned with a relatively small number of acceptors. This work develops an efficient supramolecular light-harvesting system in water, which has potential applications in dynamic luminescent materials.