A muti-modal feature fusion method based on deep learning for predicting immunotherapy response.

Immune checkpoint therapy (ICT) has greatly improved the survival of cancer patients in the past few years, but only a small number of patients respond to ICT. To predict ICT response, we developed a multi-modal feature fusion model based on deep learning (MFMDL). This model utilizes graph neural networks to map gene-gene relationships in gene networks to low dimensional vector spaces, and then fuses biological pathway features and immune cell infiltration features to make robust predictions of ICT. We used five datasets to validate the predictive performance of the MFMDL. These five datasets span multiple types of cancer, including melanoma, lung cancer, and gastric cancer. We found that the prediction performance of multi-modal feature fusion model based on deep learning is superior to other traditional ICT biomarkers, such as ICT targets or tumor microenvironment-associated markers. In addition, we also conducted ablation experiments to demonstrate the necessity of fusing different modal features, which can improve the prediction accuracy of the model.

In Situ Radical Reaction-Modified Carbon Dot Nanocapsules with Macrophage Escape and Prolonged Imaging.

Carbon dots (CDs) have emerged as an extremely promising platform for biological imaging, owing to their optical properties and low toxicity. However, one of the major challenges in utilizing CDs for in vivo imaging is their high immunogenicity and rapid clearance, which limits their potential. Herein, a novel approach for mitigating these issues is presented through the development of carbon dot nanocapsules (nCDs). Specifically, CDs are encapsulated within a zwitterionic polymer shell composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) to create nCDs with a size of ≈40 nm. Notably, the nCDs exhibit excitation-dependent photoluminescence behavior in the range of 550-600 nm, with tunability based on the excitation wavelength. In confocal imaging, CDs display a strong fluorescence signal after 8 h of incubation with phagocytes, while nCDs show minimal signal, suggesting that nCDs may be capable of evading phagocyte uptake. Furthermore, imaging studies in zebrafish demonstrate that nCDs exhibit a retention time >10 times longer than that of CDs, with fluorescence intensity remaining at 81% after 10 h compared to only 8% for CDs. Taken together, the study presents a novel approach for enhancing the performance of CDs in in vivo imaging applications, offering significant potential for clinical translation.

Exploring surface urban heat island (SUHI) intensity and its implications based on urban 3D neighborhood metrics: An investigation of 57 Chinese cities.

Excessive urban temperature exerts a substantially negative impact on urban sustainability. Three-dimensional (3D) landscapes have a great impact on urban thermal environments, while their heat conditions and driving factors still remain unclear. This study mapped urban 3D neighborhoods and their associated SUHI (surface urban heat island) intensities in summer daytime across 57 Chinese cities, and then explored their relationships, driving factors as well as implications. Nine categories of urban 3D neighborhoods existed in Chinese cities and the 3D neighborhood of High Density & Medium Rise (HDMR) contributed the largest share of urban areas. The distribution of 3D neighborhoods varied among cities due to their distinct natural and economic traits. The average SUHI intensity can amount to 4.27 °C across all Chinese 3D neighborhoods. High Density & Low Rise (HDLR) and HDMR presented higher SUHI intensities than other 3D neighborhoods in China. Urban green space (UGI) and building height (BH) had great influences on SUHI intensities. The relative contribution of UGI decreased with the increase of building density and building height, but BH presented the opposite trend. The interaction of urban 3D landscapes and function zones led to highly complicated urban thermal environments, with higher SUHI intensities in industrial zones. Besides, the SUHI intensities of 3D neighborhoods presented great diurnal and seasonal variations, with higher SUHI intensities in HDHR and HDMR at nighttime in winter and summer. What's more, urban residents may suffer unequal heat risk inside cities due to the deviations of SUHI intensities among different 3D neighborhoods. It could be a highly effective way to mitigate SUHI effects in cities by increasing urban greening and improving urban ventilation.

Circ_0000523 regulates miR-1184/COL1A1/PI3K/Akt pathway to promote nasopharyngeal carcinoma progression.

BACKGROUND: The present study is to investigate the biological functions and mechanisms of circular RNA_0000523 (circ_0000523) in nasopharyngeal carcinoma (NPC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of circ_0000523 and microRNA-1184 (miR-1184) in NPC tissues and cells. Collagen type 1 alpha 1 chain (COL1A1) expression was assessed by qRT-PCR and immunohistochemistry (IHC) assay. Cell proliferation, cell cycle progression, migration and invasion were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry and Transwell assays. Xenograft nude mouse models were used to investigate the metastatic potential of NPC cells in vivo. The binding relationships between circ_0000523 and miR-1184, and between miR-1184 and COL1A1 were detected by dual-luciferase reporter gene assay. The protein expressions of COL1A1, phosphatidylinositol 3-kinase (p85), phosphorylated (p)-p85, protein kinase B (Akt) and p-Akt were detected through Western blot. The DAVID database was used for the enrichment analysis of the potential targets of miR-1184. RESULTS: Circ_0000523 and COL1A1 mRNA expressions were significantly increased in NPC tissues and cell lines. Circ_0000523 overexpression promoted NPC cell proliferation and accelerated cell cycle progression, whereas miR-1184 overexpression reversed these effects; circ_0000523 knockdown suppressed NPC cell proliferation and induced cell cycle arrest, while miR-1184 inhibition counteracted these effects. MiR-1184 was the downstream target of circ_0000523, and COL1A1 was the target gene of miR-1184 and could be positively modulated by circ_0000523. COL1A1 overexpression increased the expression levels of p-p85 and p-Akt, whereas knocking down COL1A1 repressed their expressions. CONCLUSIONS: Circ_0000523 facilitates NPC progression through regulating the miR-1184/COL1A1 axis.

The Wound Healing Effect of Callicarpa nudiflora in Scalded Rats.

Callicarpa nudiflora has been widely used in Li nationality medicine and treated burns and scalds in China. Our objective was to preliminarily elucidate healing effect and action mechanism of Callicarpa nudiflora water extract (CNE) on the scald wounds using an experimental rat mode. The second-degree scald wounds were induced by hot water on dorsal surface of Sprague-Dawley (SD) rats, and then they were randomly divided into 5 groups as follows: control (CON), Vaseline, Silver sulfadiazine (SSD), and Vaseline supplemented with 10% and 20% CNE groups. These ointments were employed locally once daily for 21 days. The macroscopic analysis showed CNE significantly accelerated the wound healing process and lowered the wound areas on days 15, 18, and 21 especially in 20% CNE group compared to CON group. Histopathological evaluation showed the mildly hypertrophic epidermis and the intact dermis in the 20% CNE-treated group were obviously distinguished from CON group on day 21. The CNE-treated groups had no obvious effect for TNF-α and IL-10 expressions on the second day and 14th day, while TGF-ß1 expression level was decreased on the 21th day and VEGF level was increased on the 7th day in the 20% CNE group. Furthermore, the expression level of Samd3 was strongly inhibited in 20% CNE group. These findings suggested that the CNE can enhance the wound healing and skin repair in deep second-degree scald rats and thus support its traditional use.

High performance electrospun Li+-functionalized sulfonated poly(ether ether ketone)/PVA based nanocomposite gel polymer electrolyte for solid-state electric double layer capacitors.

The synthesis of a nanocomposite gel polymer electrolytes (NGPEs) using Li+-functionalized SPEEK (SPEEK(Li)) nanofiber membrane as a matrix, cross-linked PVA as a gelled agent and LiClO4 as an electrolytic salt for electric double layer capacitors (EDLCs) were reported in this work. Compared with conventional PVA based gel electrolyte, the "SO3-Li+" functional groups and the pores structure of the SPEEK(Li) nanofiber membrane improves the ionic conductivity as well as mechanical stability, which made the prepared NGPEs exhibited a high ionic conductivity of 8.9 × 10-3 S cm-1 at ambient temperature and a large voltage stability window range from 0 to 2.0 V. The fabricated symmetric EDLCs showed a specific capacitance of 146.96 F g-1 at a current density of 0.5 A g-1, with a maximum energy density of 18.26 W h kg-1. Meanwhile, the EDLCs showed outstanding cyclical stability of 98% specific capacitance retention after 3000 cycles GCD testing, all of these results indicated that the NGPEs should be appropriate to EDLCs and next-generation energy storage systems.

Effect of Alpinia officinarum Hance alcohol extracts on primary dysmenorrheal.

OBJECTIVE: To study the effect of Alpinia officinarum Hance (A. officinarum) 80% alcohol extract on the primary dysmenorrhea. METHODS: A. officinarum 80% alcohol extract were enriched by macroporous adsorption resins. Female mice of primary dysmenorrhea model were established by oxytocin induction; the effects of A. officinarum 80% alcohol extract on primary dysmenorrhea were observed by body twist method; and the homogenate level of prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2) and Ca(2+) in the uterus were observed in oxytocin-induced female mice. RESULTS: The writhing frequency of primary dysmenorrhea mice was significantly decreased after treatment of A. officinarum 80% alcohol extract and the level of PGF2α, PGE2 and Ca(2+) in mice uterus was significantly decreased (P < 0.05, P < 0.01) in groups of mice treated with middle and high dosage of A. officinarum 80% alcohol extract compared with that of model group. CONCLUSIONS: These findings suggest that A. Officinarum 80% alcohol extract can significantly relieve primary dysmenorrhea.

The protective effects of puerarin in cardiomyocytes from anoxia/reoxygenation injury are mediated by PKCε.

Puerarin is an isoflavone isolated from traditional Chinese medicine Ge-gen (Radix Puerariae). Clinical studies have confirmed the cardioprotective effects of puerarin; however, the mechanisms underlying these effects are still unclear. On the basis of previous findings, we hypothesized that puerarin protects cardiomyocytes from ischemia-reperfusion injury via the protein kinase C epsilon (PKCε) (a critical cardioprotective protein) signalling pathway. Neonatal rat primary cardiomyocytes were preconditioned with puerarin or puerarin plus εV1-2, a selective PKCε inhibitor, prior to anoxia/reoxygenation (A/R) treatment. Western blot analysis showed that expression and activity of PKCε protein in puerarin preconditioned group were both increased compared with the control or A/R group. Subsequent assays showed that preconditioning with puerarin could increase the viability of neonatal rat primary cardiomyocytes treated with A/R, decreased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, cell necrosis and apoptosis induced by A/R injury. However, the protective effects of puerarin completely disappeared in the group pretreated with puerarin plus εV1-2. Thus, for the first time, we revealed the protective effects of puerarin in cardiomocytes from anoxia/reoxygenation injury are mediated by PKCε.

The effects of quercetin protect cardiomyocytes from A/R injury is related to its capability to increasing expression and activity of PKCε protein.

Quercetin is a ubiquitous flavonoid found in vegetable foods. Epidemiological and animal studies have reported an inverse association between quercetin intakes and occurrence and development of various cardiovascular diseases. Some researchers have inferred that the mechanisms of quercetin to protect cardiomyocytes from ischemia/reperfusion injury may be involved in modulation of intracellular signal pathways and regulation of proteins expression beyond its antioxidant activity. The aim of this study was to investigate whether quercetin protect cardiomyocytes from anoxia/reoxygenation injury through PKCε pathway. Neonatal rat primary cardiomyocytes were pretreated with quercetin or quercetin plus εV1-2, a selective PKCε inhibitor, prior to A/R treatment. Western blotting analysis showed that the level of PKCε and phosphor-PKCε Ser297 in the quercetin pretreatment group were all increased significantly compared to the control or A/R group. Subsequent assays showed that pretreated with quercetin could increase the viability of neonatal rat primary cardiomyocytes suffered A/R, decrease the apoptosis and ROS and alleviate the loss of mitochondrial membrane potential induced by A/R injury. However, the protective effects of quercetin disappeared in the group pretreated with εV1-2. Thus, for the first time, we revealed that one of the mechanisms of quercetin protecting cardiomyocytes from A/R injury might be increase the expression of PKCε protein and then enhance the activity of its downstream pathway.