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Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.

Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer, the leading cancer-related death worldwide. Nucleolar spindle-associated protein 1 (NUSAP1) is a microtubule-associated protein firstly been found in proliferating cells, and recently known to be involved in carcinogenesis. However, the role of NUSAP1 in LUAD has yet to be explored. In current study, we used GEO datasets to identified a group of hub genes in LUAD, used Kaplan-Meier analysis to explore their impact on prognosis. NUSAP1 was chosen based on clinical relevance and literature searching results. The expression level of NUSAP1 was explored using TIMER, TCGA-LUAD database, human protein atlas (HPA), and verified by immunohistochemistry. Genes co-expressed with NUSAP1 were identified and GO/KEGG were performed to identify its biological functions. The impact of NUSAP1 on immune infiltration was investigated in TIMER. The correlation between NUSAP1 expression and clinical relevance were identified using diagnostic receiver operating characteristic (ROC) curves, nomogram model, and cox regression analysis. Immunohistochemistry was used to confirm the over-expression of NUSAP1 in LUAD and its correlation with MDSC. In short, we found a group of 20 hub genes in LUAD, all of which were differentially expressed in LUAD and most of them predicted a poor prognosis. NUSAP1 was upregulated in LUAD and most of the malignancies and correlated to multiple clinical parameters like pathological stage, N stage, M stage. Co-expressed genes and GO/KEGG showed that NUSAP1 mainly participates in cell cycle. Immune infiltration study demonstrated that NUSAP1 correlated to multiple immune cells, particularly myeloid-derived suppressor cell (MDSC). PrognoScan database verified the prognostic value of NUSAP1. Lastly, high expression of NUSAP1 and its correlation with MDSC was testified by immunohistochemistry. In summary, we found NUSAP1 were upregulated in LUAD and can serve as potential biomarker to indicate prognosis of LUAD.

3D rendering of a HCT 116 tumor spheroid over 21 days.

Fig. S1. RNF6 genomic amplification is prevalent in colorectal cancer and correlated with shortened patient survival. Fig. S2. RNF6 is clinically relevant in colorectal cancer. Fig. S3. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in RNF6-higher/lower expression CRC cells and patients, and RNF6 is an oncogenic gene. FigureS4. RNF6 upregulates pSTAT3 via downregulating SHP-1 expression. Figure S5. RNF6 Interacts with SHP-1 and enhances ubiquitylation and degradation of SHP-1. Figure S6. Effectiveness of pSTAT3 inhibitors in treating RNF6-amplified tumors.

Supplementary Material and Methods clean

Fig. S1. RNF6 genomic amplification is prevalent in colorectal cancer and correlated with shortened patient survival. Fig. S2. RNF6 is clinically relevant in colorectal cancer. Fig. S3. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in RNF6-higher/lower expression CRC cells and patients, and RNF6 is an oncogenic gene. FigureS4. RNF6 upregulates pSTAT3 via downregulating SHP-1 expression. Figure S5. RNF6 Interacts with SHP-1 and enhances ubiquitylation and degradation of SHP-1. Figure S6. Effectiveness of pSTAT3 inhibitors in treating RNF6-amplified tumors.

Distribution of necrotic tissue in a HCT 116 tumor spheroid over time.

Table S1.Expression of human ubiquitin ligase genes in 246 CRC patients of TCGAdatabase.TableS2.Clinial information of 62 cases CRC patients (fresh tissues).Table S3.Clinial information of 78 cases CRC patients (paraffin tissues).Table S4.Clinial information of 97 cases CRC patients (paraffin tissues).Table S5.RNA sequence data. TableS 6. Primer sequences

Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anticancer drug development. However, currently available imaging approaches used in high-throughput screening drug discovery platforms, for example, bright-field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, noninvasive optical coherence tomography (OCT) imaging platform to characterize 3D morphologic and physiologic information of multicellular tumor spheroids (MCTS) growing from approximately 250 to 600 μm in height over 21 days. In particular, tumor spheroids of two cell lines, glioblastoma (U-87MG) and colorectal carcinoma (HCT116), exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphologic and physiologic features of MCTS, showing great potential for high-throughput drug screening. Cancer Res; 77(21); 6011–20. ©2017 AACR.

3D rendering of an U-87 MG tumor spheroid over 21 days.

Objective: The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer. We aimed to explore the mechanical, biological, and clinical role of RNF6 in colorectal cancer initiation and progression.Design: The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real-time PCR, Western blot, and immunohistochemical staining. Gene expression profiling studies were performed to identify pivotal genes regulated by RNF6. Biological function of RNF6 on tumor growth and metastasis was detected in vivo and in vitro. Role of RNF6 in modulating SHP-1 expression was examined by coimmunoprecipitation and confocal microscopy, respectively.Results: The copy number of RNF6 was significantly amplified in colorectal cancer, and the amplification was associated with RNF6 expression level. Amplification and overexpression of RNF6 positively correlated with patients with colorectal cancer with poor prognosis. The gene set enrichment analysis (GSEA) revealed cell proliferation, and invasion-related genes were enriched in RNF6 high-expressed colorectal cancer cells as well as in patients from TCGA dataset. Downregulation of RNF6 impaired the colorectal cancer cell proliferation and invasion in vitro and in vivo. RNF6 may activate the JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1.Conclusions: Genomic amplification drives RNF6 overexpression in colorectal cancer. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors. Clin Cancer Res; 24(6); 1473–85. ©2017 AACR.

Supplementary Video 3 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Figure 1, Legends for Figure 1 and Videos 1-4 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 1 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Supplementary Video 2 from Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

BACKGROUND Diabetes has become a severe health threat in China, owing to its increasing prevalence, long-term morbidity, and mortality. OBJECTIVE This study evaluated the association between adherence to blood glucose self-monitoring guidance and glycemic control among patients with T2DM A 12-week mHealth-based prospective cohort study was conducted. Patients received recommendations on self-monitoring of blood glucose (SMBG) testing frequencies and uploaded testing results through smart glucose monitoring devices. initiating basal insulin in China. METHODS A 12-week mHealth-based prospective cohort study was conducted. Patients received recommendations on self-monitoring of blood glucose (SMBG) testing frequencies and uploaded testing results through smart glucose monitoring devices. RESULTS A total of 14,084 patients from 242 hospitals were enrolled. Most patients (73.3%) had 9%. The benefit of improving adherence to SMBG guidance was consistently found for FBG reduction, HbA1c, and FBG target rate. CONCLUSIONS The study demonstrated a positive relationship between adherence and glycemic control and identified patient characteristics with poorer adherence for further customization of mHealth.

Whether it is for military or civilian use, quadrotor UAV has always been one of research central issues. Most of the current quadrotor drones are manually operated and use GPS signals for navigation, which not only limits the operating range of the drone but also consumes a lot of manpower and material resources. This research mainly studies the method of realizing autonomous flight and conflict avoidance of quadrotor UAV by using multisensor system and deep learning method in extreme flight conditions through track prediction. The convolutional neural network method is used to extract the image information collected by the UAV sensor system. And it uses the cyclic neural network to extract the time feature of the information collected by the UAV sensor. The research results show that the track prediction method based on the deep learning method has higher flight accuracy for quadrotor UAVs. The yaw error of the spatial position is only 2.82%, and the maximum error of the time characteristic error tolerance is only 0.77%.

The current study explores the possibility of using the coolant injected from the near tip suction side of a turbine blade to reduce the tip leakage loss. Each case studied has a cooling hole injecting a coolant stream. To model the mixing of the coolant at different axial locations, each of four cases is investigated with a cooling hole located at 10% blade axial chord [Formula: see text], 20% [Formula: see text], 30% [Formula: see text] or 40% [Formula: see text] from the leading edge. In computational fluid dynamics simulation, the exit area of the cooling hole is defined with mass flow inlet boundary condition to simulate a coolant injection. It is found that the tip leakage loss of the case with a cooling hole located at 10% [Formula: see text] is the lowest and is 3.2% lower than that of the uncooled baseline case. The tip leakage loss increases as the cooling hole located further downstream. For the case with cooling hole at 40% [Formula: see text], the loss is 1.5% higher than the uncooled baseline case. The effect of the blowing ratio on the tip leakage loss is also investigated. For the case with the cooling hole located at 10% [Formula: see text], the tip leakage loss first decreases and then increases as the blowing ratio increases. When the tip leakage loss of one case is less than that of baseline case, it is found that mixing of the coolant and the low-energy fluid in the tip leakage vortex core reduces the stagnation pressure difference between mainstream and the fluid within the vortex core, and thus reducing the mixing loss within the blade passage.

Inorganic/organic dielectric composites with outstanding energy storage properties at a low electric field possess the advantages of low operating voltage and small probability of failure. Composites filled with two-dimensional inorganic nanosheets have attracted much attention owing to their fewer interfacial defects caused by the agglomeration of fillers. Continuous oxide films with a preferred orientation can play a significant role in enhancing energy storage. The challenge is to prepare large-sized, freestanding, single-crystal, ferroelectric oxide films and to combine them with polymers. In this work, a well-developed water-dissolvent process was used to transfer millimeter-sized (100)-oriented BaTiO

In higher plants, sucrose synthase (Susy, EC 2.4.1.13) as an enzyme with a core function, involved in the synthesis and breakdown of sugars, and plays an important role in growth and metabolism. Although, the different genes encoding Susy isozyme proteins have been cloned and functionally verified in several plant species, to date detailed information about the Susy genes is lacking in Sorghum. Here, we demonstrated the identification of five novel Susy genes from the sorghum genome database. Sequence, structure and phylogenetic analyses of these five SbSusy genes revealed evolutionary conservation through Susy gene family members across Sorghum and other crop plants. The expression of sorghum Susy genes was investigated via transcriptome database in various developmental stages and different tissues. Further qRT-PCR was performed to reveal the induction of SbSusy genes under salt, drought and sugar induction. The results indicated that all Susy genes were differentially expressed in various tissues and highly associated with sucrose metabolism. This study shows a theoretical reference of Susy genes in Sorghum, which provides new insights for the knowledge of the evolution relationships, and basic information to help clarify the molecular mechanism of Susy synthase genes in Sorghum. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-022-01166-8.