Gold nanoparticle-decorated fluorine-doped tin oxide substrate for sensitive label-free OIRD microarray chips.

Oblique incidence reflectance difference (OIRD) is an emerging technique enabling real-time and label-free detection of bio-affinity binding events on microarrays. The interfacial architecture of the microarray chip is critical to the performance of OIRD detection. In this work, a sensitive label-free OIRD microarray chip was developed by using gold nanoparticle-decorated fluorine-doped tin oxide (AuNPs-FTO) slides as a chip substrate. This AuNPs-FTO chip demonstrates a higher signal-to-noise ratio and improved sensitivity compared to that built on FTO glass, showing a detection limit of as low as 10 ng mL-1 for the model target, HRP-conjugated streptavidin. On-chip ELISA experiments and optical calculations suggest that the enhanced performance is not only due to the higher probe density enabling a high capture efficiency toward the target, but most importantly, the AuNP layer arouses optical interference to improve the intrinsic sensitivity of OIRD. This work provides an effective strategy for constructing OIRD-based microarray chips with enhanced sensitivity, and may help extend their practical applications in various fields.

Vina-FPGA-Cluster: Multi-FPGA Based Molecular Docking Tool with High-Accuracy and Multi-Level Parallelism.

AutoDock Vina (Vina) stands out among numerous molecular docking tools due to its precision and comparatively high speed, playing a key role in the drug discovery process. Hardware acceleration of Vina on FPGA platforms offers a high energy-efficiency approach to speed up the docking process. However, previous FPGA-based Vina accelerators exhibit several shortcomings: 1) Simple uniform quantization results in inevitable accuracy drop; 2) Due to Vina's complex computing process, the evaluation and optimization phase for hardware design becomes extended; 3) The iterative computations in Vina constrain the potential for further parallelization. 4) The system's scalability is limited by its unwieldy architecture. To address the above challenges, we propose Vina-FPGA-cluster, a multi-FPGA-based molecular docking tool enabling high-accuracy and multi-level parallel Vina acceleration. Standing upon the shoulders of Vina-FPGA, we first adapt hybrid fixed-point quantization to minimize accuracy loss. We then propose a SystemC-based model, accelerating the hardware accelerator architecture design evaluation. Next, we propose a novel bidirectional AG module for data-level parallelism. Finally, we optimize the system architecture for scalable deployment on multiple Xilinx ZCU104 boards, achieving task-level parallelism. Vina-FPGA-cluster is tested on three representative molecular docking datasets. The experiment results indicate that in the context of RMSD (for successful docking outcomes with metrics below 2Å), Vina-FPGA-cluster shows a mere 0.2% lose. Relative to CPU and Vina-FPGA, Vina-FPGA-cluster achieves 27.33× and 7.26× speedup, respectively. Notably, Vina-FPGA-cluster is able to deliver the 1.38× speedup as GPU implementation (Vina-GPU), with just the 28.99% power consumption.

Porcine Granulosa-Cell-Derived Exosomes Enhance Oocyte Development: An In Vitro Study.

Recent studies have established that exosomes (EXs) derived from follicular fluid (FF) can promote oocyte development. However, the specific sources of these EXs and their regulatory mechanisms remain elusive. It is universally acknowledged that oocyte development requires signal communication between granulosa cells (GCs) and oocytes. However, the role of GC-secreted EXs and their functions are poorly understood. This study aimed to investigate the role of porcine granulosa-cell-derived exosomes (GC-EXs) in oocyte development. In this study, we constructed an in vitro model of porcine GCs and collected and identified GC-EXs. We confirmed that porcine GCs can secrete EXs and investigated the role of GC-EXs in regulating oocyte development by supplementing them to cumulus-oocyte complexes (COCs) cultured in vitro. Specifically, GC-EXs increase the cumulus expansion index (CEI), promote the expansion of the cumulus, alleviate reactive oxygen species (ROS), and increase mitochondrial membrane potential (MMP), resulting in improved oocyte development. Additionally, we conducted small RNA sequencing of GC-EXs and hypothesized that miR-148a-3p, the highest-expressed microRNA (miRNA), may be the key miRNA. Our study determined that transfection of miR-148a-3p mimics exerts effects comparable to the addition of EXs. Meanwhile, bioinformatics prediction, dual luciferase reporter gene assay, and RT-qPCR identified DOCK6 as the target gene of miR-148a-3p. In summary, our results demonstrated that GC-EXs may improve oocyte antioxidant capacity and promote oocyte development through miR-148a-3p by targeting DOCK6.

Label-Free and Real-Time Optical Detection of Affinity Binding of the Antibody on Adherent Live Cells.

Oblique-incidence reflectivity difference (OIRD) is a novel real-time, label-free, and nondestructive optical detection method and exhibits encouraging application in the detection of antibody/DNA microarrays. In this study, for the first time, an OIRD label-free immunoassay was achieved by using adherent live cells as the probe. The cells were cultured on glass cells, and the affinity binding of antibodies targeted on the HLA class I antigen of the cell surface was detected with an OIRD. The results show that an OIRD is able to detect the binding process of anti-human HLA-A, B, and C antibodies on MDA-MB-231 cells and HUVEC cells. Control experiments and complementary fluorescence analysis confirmed the high detection specificity and good quantitative virtue of the OIRD label-free immunoassay. Label-free OIRD imaging analysis of cell microarrays was further demonstrated successfully, and the underlying optical mechanism was revealed by combining the theoretical modeling. This work explores the use of live cells as probes for an OIRD immunoassay, thus expanding the potential applications of the OIRD in the field of pathological analysis, disease diagnosis, and drug screening, among others.

Optical Approach for Mapping the Intercalation Capacity of Porous Electrodes.

The intercalation capacity of a porous electrode in real batteries is not uniform spatially due to the inevitable structural and compositional inhomogeneity and site-dependent ion and electron transport features. Reliable methods to quantify the capacity distribution are highly desirable but absent so far in battery research. In this paper, a novel optical technique, oblique incident reflection difference (OIRD), was employed to monitor in situ the electrochemical ion (de)intercalation behavior of Prussian blue analogue (PBA) porous films. The OIRD signal responded synchronously to the ion (de)intercalation, and the change in the OIRD signal (ΔI) was positively correlated with the local electrochemical capacity, thereby enabling mapping of the spatially resolved ion storage capacity of the films. Optical analysis further showed that the OIRD response originated from the ion (de)intercalation-induced dielectric constant change of PBA films. This work therefore offers an intriguing in situ and spatially resolved tool for the study of rechargeable batteries.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

All-optical self-manipulation of light flow in on-chip topological waveguides based on synthetic dimension.

Topological photonic crystals provide a new platform for designing nanophotonic devices with robustness. Especially, all-optical devices, which use the light controlling light, based on nonlinear topological photonic crystals, have not been reported yet. In this article, we numerically investigate the robust self-manipulation of light flow in silicon topological photonic crystal waveguides based on the Kerr nonlinearity of silicon and topological edge states of photonic crystal waveguides. By adjusting the intensity of incident light at a communication wavelength of 1550 nm, the transmission path of the light flow in waveguides can be effectively controlled, and such manipulation is immune to some disturbances of nanostructures and thus shows the robustness. The results indicate that nonlinear topological photonic crystals have potential applications in on-chip integrated all-optical photonic devices.

Non-fouling polymer brush grafted fluorine-doped tin oxide enabled optical and chemical enhancement for sensitive label-free antibody microarrays.

Oblique-incidence reflectivity difference (OIRD) is a compelling technique for real-time, label-free and non-destructive detection of antibody microarray chips, but its sensitivity needs essential improvement for clinical diagnosis. In this study, we report an innovative high-performance OIRD microarray by using poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) brush grafted fluorine-doped tin oxide (FTO) as the chip substrate. The polymer brush enhances the interfacial binding reaction efficiency of targets from the complicated sample matrix due to its high antibody loading and excellent anti-fouling merits; the FTO-polymer brush layered structure, on the other hand, excites the interference enhancement effect of OIRD to achieve enhanced intrinsic optical sensitivity. Synergistically, the sensitivity of this chip is significantly improved compared to rival chips, achieving a limit of detection (LOD) as low as 25 ng mL-1 for the model target C-reactive protein (CRP) in 10% human serum. This work explores the tremendous influence of the chip interfacial structure on the OIRD sensitivity and proposes a rational interfacial engineering strategy to boost the performance of the label-free OIRD based microarray and other bio-devices.

Vision Measurement Method Based on Plate Glass Window Refraction Model in Tunnel Construction.

Due to the harsh environment of high humidity and dust in tunnel construction, the vision measurement system needs to be equipped with an explosion-proof glass protective cover. The refractive effect of the plate glass window invalidates the pinhole model. This paper proposes a comprehensive solution for addressing the issue of plane refraction. First, the imaging model for non-parallel plane refraction is established based on dynamic virtual focal length and the Rodriguez formula. Further, due to the failure of the epipolar constraint principle in binocular vision systems caused by plane refraction, this paper proposes the epipolar constraint model for independent refractive plane imaging. Finally, an independent refraction plane triangulation model is proposed to address the issue of triangulation failure caused by plane refraction. The RMSE of the depth of field errors in the independent refraction plane triangulation model is 2.9902 mm before correction and 0.3187 mm after correction. The RMSE of the positioning errors before and after correction are 3.5661 mm and 0.3465 mm, respectively.

Label-free OIRD microarray chips with a nanostructured sensing interface: enhanced sensitivity and mechanism.

Oblique-incidence reflectivity difference (OIRD) is a novel optical technique for protein microarray detection with the characteristics of being real-time, label-free, high-throughput and compatible with arbitrary chip substrates. It is necessary yet challenging to improve the sensitivity of the OIRD microarray and gain a clear understanding of the enhancement mechanism for practical applications. In this study, we report a microarray chip specifically designed for OIRD to improve its sensitivity by using an electrochemically etched nanostructured fluorine-doped tin oxide (FTO) slide as the substrate. Compared with chips printed on a conventional glass slide and pristine FTO, the OIRD sensitivity and signal-to-noise ratio of this microarray are significantly improved, reaching a limit of detection (LOD) as low as 50 ng mL-1 for the streptavidin target in 10% human serum, which is one order of magnitude lower than that of the glass-based chip. On-chip ELISA and theoretical calculation reveal that the enhanced sensitivity is not only because of its higher capture efficiency towards the target, but also benefits from the optical enhancement enabled by its unique nanostructured sensing interface. This work provides a new universal strategy for designing high performance OIRD-based chips via rational interfacial engineering, thus paving the way to a label-free OIRD immunoassay and real-time analysis of biomolecular interactions.

Spatiotemporal Mapping of Extracellular Electron Transfer Flux in a Microbial Fuel Cell Using an Oblique Incident Reflectivity Difference Technique.

Extracellular electron transfer (EET) is a critical process involved in microbial fuel cells. Spatially resolved mapping of EET flux is of essential significance due to the inevitable spatial inhomogeneity over the bacteria/electrode interface. In this work, EET flux of a typical bioanode constructed by inhabiting Shewanella putrefaciens CN32 on a porous polyaniline (PANI) film was successfully mapped using a newly established oblique incident reflectivity difference (OIRD) technique. In the open-circuit state, the PANI film was reduced by the electrons released from the bacteria via the EET process, and the resultant redox state change of PANI was sensitively imaged by OIRD in a real-time and noninvasive manner. Due to the strong correlation between the EET flux and OIRD signal, the OIRD differential image represents spatially resolved EET flux, and the in situ OIRD signal reveals the dynamic behavior during the EET process, thus providing important spatiotemporal information complementary to the bulky electrochemical data.

Short O-GlcNAcase Is Targeted to the Mitochondria and Regulates Mitochondrial Reactive Oxygen Species Level.

O-GlcNAcylation is a reversible post-translational modification involved in the regulation of cytosolic, nuclear, and mitochondrial proteins. Only two enzymes, OGT (O-GlcNAc transferase) and OGA (O-GlcNAcase), control the attachment and removal of O-GlcNAc on proteins, respectively. Whereas a variant OGT (mOGT) has been proposed as the main isoform that O-GlcNAcylates proteins in mitochondria, identification of a mitochondrial OGA has not been performed yet. Two splice variants of OGA (short and long isoforms) have been described previously. In this work, using cell fractionation experiments, we show that short-OGA is preferentially recovered in mitochondria-enriched fractions from HEK-293T cells and RAW 264.7 cells, as well as mouse embryonic fibroblasts. Moreover, fluorescent microscopy imaging confirmed that GFP-tagged short-OGA is addressed to mitochondria. In addition, using a Bioluminescence Resonance Energy Transfer (BRET)-based mitochondrial O-GlcNAcylation biosensor, we show that co-transfection of short-OGA markedly reduced O-GlcNAcylation of the biosensor, whereas long-OGA had no significant effect. Finally, using genetically encoded or chemical fluorescent mitochondrial probes, we show that short-OGA overexpression increases mitochondrial ROS levels, whereas long-OGA has no significant effect. Together, our work reveals that the short-OGA isoform is targeted to the mitochondria where it regulates ROS homoeostasis.

Self-transformation synthesis of hierarchically porous benzene-bridged organosilica nanoparticles for efficient drug delivery.

Herein, a feasible outside-in hydrothermal self-transformation strategy is presented to fabricate hierarchically porous benzene-bridged organosilica nanoparticles (HPBONs), and detailed mechanistic investigations were performed to study the formation of hierarchically porous nanostructures. The obtained HPBONs consisted of a mesoporous core (2.3 nm) and a large mesoporous flocculent shell (12.6 nm), which corresponded to an overall diameter of âˆ¼ 200 nm and good water dispersibility, respectively. Owing to the unique hierarchically porous structure and high surface area (877 m2/g), HPBONs showed a high coloading capacity for the hydrophilic drug doxorubicin (DOX) and the hydrophobic photosensitizer chlorin e6 (Ce6) (355 µg/mg, 38 µg/mg, respectively) and acid-responsive DOX drug release (42.62%), leading to precise chemo-photodynamic therapy in vitro, as the cytotoxicity assay revealed 70% killing of breast cancer (MCF-7) cells. This research provides a new method to construct hierarchically porous organosilica-based nanodelivery systems.

The protective effect of isoflurane pretreatment on liver IRI by suppressing noncanonical pyroptosis of liver macrophages.

BACKGROUND: Liver ischaemia-reperfusion injury (IRI) is a major complication in the perioperative period and often leads to liver failure and even systemic inflammation. Sufficient evidence has demonstrated that isoflurane has anti-inflammatory effects. We aimed to determine whether isoflurane pretreatment protects against liver IRI and to investigate the mechanisms involved in this protection. METHODS: Male C57BL/6 mice were pretreated with or without isoflurane and subjected to 90 min of 70% liver ischaemia, followed by reperfusion for 6 h. Liver tissues and serum were analysed to assess liver IRI. To probe the mechanisms, liver macrophages isolated from C57BL/6 mice were pretreated with or without emulsified isoflurane for 30 min before incubation with 1 µg/ml lipopolysaccharide (LPS) for 24 h. Inflammatory cytokine production, intracellular Ca2+ levels, caspase-11 expression, NF-κB transcription, and NLRP3 inflammasome activation were assessed by ELISA, an intracellular Ca2+ concentration assay, immunohistochemistry, or Western blotting. RESULTS: Isoflurane preconditioning significantly relieved liver IRI in mice and LPS-induced inflammation in liver macrophages. Additionally, isoflurane pretreatment inhibited caspase-11 expression and noncanonical pyroptosis-related production of cytokines (IL-1ß and IL-18). Interestingly, isoflurane preconditioning reduced intracellular Ca2+ levels, NF-κB translocation, and NLRP3 inflammasome activation in LPS-induced macrophages. Our results indicated that isoflurane preconditioning ameliorated liver IRI by suppressing noncanonical pyroptosis in liver macrophages. These findings suggest that isoflurane could be a pharmacological agent for liver IRI prevention and thus deserves more attention and further investigation.

SCARF1 promotes M2 polarization of Kupffer cells via calcium-dependent PI3K-AKT-STAT3 signalling to improve liver transplantation.

OBJECTIVES: This study aimed to investigate the protective effect of SCARF1 on acute rejection (AR), phagocytic clearance of Kupffer cells (KCs), M2 polarization and the exact mechanism underlying these processes. METHODS: AAV was transfected into the portal vein of rats, and AR and immune tolerance (IT) models of liver transplantation were established. Liver tissue and blood samples were collected. The level of SCARF1 was detected via WB and immunohistochemical staining. Pathological changes in liver tissue were detected using HE staining. Apoptotic cells were detected using TUNEL staining. KC polarization was assessed via immunohistochemical staining. Primary KCs were isolated and co-cultured with apoptotic T lymphocytes. Phagocytosis of apoptotic cells and polarization of KCs were both detected using immunofluorescence. Calcium concentration was determined using immunofluorescence and a fluorescence microplate reader. The levels of PI3K, p-AKT and P-STAT3 were assessed via WB and immunofluorescence. RESULTS: Compared to the IT group, the level of SCARF1 was significantly decreased in the AR group. Overexpression of SCARF1 in KCs improved AR and liver function markers. Enhanced phagocytosis mediated by SCARF1 is beneficial for improving the apoptotic clearance of AR and promoting M2 polarization of KCs. SCARF1-mediated enhancement of phagocytosis promotes increased calcium concentration in KCs, thus further activating the PI3K-AKT-STAT3 signalling pathway. CONCLUSIONS: SCARF1 promotes the M2 polarization of KCs by promoting phagocytosis through the calcium-dependent PI3K-AKT-STAT3 signalling pathway.

Structural property-induced different phonon-twin-boundary scattering in diamond.

Twin boundaries (TBs), as one kind of crystal defect, have often been observed in various material systems, and the (111)/[110] TB has been verified to show weak phonon scattering. However, it's still not clear whether other TBs can show similar thermal properties to the (111)/[110] TB. To solve this issue, in this work, we perform a systematic study of heat transport across six kinds of twin boundaries in diamond, including the (111)/[110], (221)/[110], (331)/[110], (113)/[110], (112)/[110] and (310)/[001] TBs, by both molecular dynamics simulations and first-principles calculations. The results indicate that the thermal boundary resistance of the six TBs ranges from 1.01 × 10-11 to 6.35 × 10-10 m2 K W-1; specifically, the (111)/[110] TB shows much weaker phonon scattering than the others. The different phonon scattering at TBs mainly depends on the transmission coefficients across the twin boundaries for boundaries with the same symmetry, as well as the combined action of group velocity and phonon mean free path. Furthermore, by analyzing the structural properties of TBs, it can be observed that TB thermal resistance varies significantly with the TB structure, and is strongly correlated with TB energy and bond difference parameter. Our findings will provide useful guidelines for designing efficient thermoelectric and thermal management materials based on phonon-TB scattering.

C2orf40 inhibits hepatocellular carcinoma through interaction with UBR5.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) urgently needs a marker for early diagnosis and targeted treatment. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the precise role and regulatory mechanism by C2orf40 contribute to HCC remain elusive and merit exploration. METHODS: Reverse-transcription PCR, quantitative real-time PCR, and methylation-specific PCR were used to detect expression and methylation of C2orf40 in HCC cell lines or tissues. The effects of C2orf40 in liver cancer cells were examined via colony formation, CCK8, transwell, and flow cytometric assays. The effect of C2orf40 on tumorigenesis in vivo was determined by xenografts and immunohistochemical analysis. Western blot, indirect immunofluorescence, Co-IP, and cycloheximide (CHX) were used to further investigate the potential mechanism of C2orf40. RESULTS: The down-regulation of C2orf40 in hepatocellular cancer tissue samples is often related to the degree of methylation of its promoter CpG. The recovery of C2orf40 expression in HCC cell lines can induce G0/G1 phase arrest and apoptosis and also inhibit cell migration and invasion by reversing the epithelial-mesenchymal transition (EMT) process, both in vivo and in vitro. In addition, C2orf40 can increase the expression of p21 through interaction with UBR5. CONCLUSIONS: Low expression levels of C2orf40 are related to the hypermethylation of its promoter. C2orf40 can inhibit HCC through UBR5-dependent or p53-independent mechanisms. C2orf40 may be a diagnostic biomarker and a potential therapeutic target in HCC.

Effect of TRAF1 on Phenotypic Changes Of Kupffer Cells In Liver Transplantation Ischemic-Reperfusion.

OBJECTIVE: The purpose of this study was to explore the effect of TRAF1 on phenotypic changes of KCs in I/R in liver transplantation. METHODS: SD rats were randomly divided into sham group and liver transplantation I/R group. KCs were extracted from rat livers in each group. KCs were transfected by lentivirus of si-TRAF1 or si-HOIP, and induced by Lipopolysaccharide (LPS). Flow cytometry was used to detect cell apoptosis. Western blot and RT-PCR were used to detect the protein and mRNA expression levels. RESULTS: Compared with the sham group, the expression levels of TRAF1, TNF-α and IL-1ß were significantly increased in the I/R group (P<0.05). In addition, compared with the control group, the expression levels of NF-κB (P65 and p-P65) and M1 phenotype (TNF-α and IL-1ß) were notably increased in si-TRAF1 and si-HOIP group (all P<0.05). Furthermore, the levels of Linear Ubiquitin Complex (LUBAC) were markedly increased in LPS-induced KCs in comparison with the control group (P<0.05). Moreover, compared with the control group, the expression levels of P65, p-P65, TNF-α and IL-1ß were notably decreased in the si-TRAF1 and si-HOIP group (P<0.05). The expression levels of P65, p-P65, TNF-α and IL-1ß were significantly increased in si-TRAF1 and si-HOIP group when compared to the control group (P<0.05). CONCLUSION: TRAF1 was an important negative regulator of liver transplantation I/R by inhibiting the activation of NF-κB in KCs and preventing its M1 phenotype transformation.

General and facile syntheses of hybridized deformable hollow mesoporous organosilica nanocapsules for drug delivery.

Deformable materials have garnered widespread attention in biomedical applications. Herein, a controllable, general, and simple alkaline etching strategy was used to synthesize deformable hollow mesoporous organosilica nanocapsules (DMONs), in which multiple organic moieties were homogeneously incorporated into the framework. DMONs with double-, triple-, and even quadruple-hybridized frameworks were prepared by the selective introduction of organosilica precursors in accordance with the chemical homology principle through a surfactant-directed sol-gel procedure and a subsequent etching process in alkaline solution. The triple-hybridized DMONs possessed uniform and controllable diameters (100-330 nm), and large hollow cavities (50-270 nm). Liquid cell electron microscopy images demonstrated that the DMONs were deformable in solution. Elemental mapping images suggested that the organic components were homogeneous distribution within the entire DMONs framework. Statistical analysis of cell proliferation assays showed that breast cancer MCF-7 viability exceeded 85% when the cells are incubated with the triple-hybridized DMONs (800 µg mL-1) for 24 h. Histological assessments of main organs indicated no tissue injury or necrosis after intravenous injection of the DMONs 7 days (5 mg kg-1 body weight). Quantitative analysis indicated that the cellular uptake of the DMONs was 6-fold higher than that of their hard counterparts when the number of nanoparticles added was 1.25 × 104, and similar results were found for 4 T1 cells. Furthermore, doxorubicin (DOX) loaded triple-hybridized DMONs with a loading efficiency of 16.9 wt%, produced a strong killing effect on tumor cells. Overall, DMONs with various incorporated organic functional groups could serve as novel nanoplatforms for drug delivery in biomedical applications.

Nogo-B fosters HCC progression by enhancing Yap/Taz-mediated tumor-associated macrophages M2 polarization.

Tumor-associated macrophages (TAMs) and their M2-type extremely promote tumor angiogenesis, invasion and metastasis, including hepatocellular carcinoma (HCC). Nogo-B is expressed in most tissues and participates in macrophage polarization. However, whether Nogo-B is involved in the polarization and the effects of TAMs has been unclear. The expression of Nogo-B in TAMs of HCC patients is significantly increased, which correlated with the poor prognosis of the patients with HCC. Coincidentally, HCC conditioned medium (HCM) facilitated Nogo-B expression and the M2 phenotype of macrophages. Nogo-B knockdown Nogo-B significantly suppressed the M2-type polarization of macrophages and inhibited HCC cells proliferation both in vivo and in vitro. Furthermore, interference of Nogo-B facilitates macrophage-mediated apoptosis of tumor cells. Nogo-B meaningfully enhanced IL4-stimulated the alternative activation of macrophages as well as expression of the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz). An inhibitor of Yap, Verteporfin, could block Nogo-B-Yap/Taz-mediated macrophages M2 polarization. Nogo-B expression in macrophages facilitates tumor-associated macrophages M2 polarization and protumoral effects of TAMs in HCC. Targeting Nogo-B/Yap/Taz in macrophages could provide a new therapeutic strategy in HCC therapy.