Topoisomerase II trapping agent teniposide induces apoptosis and G2/M or S phase arrest of oral squamous cell carcinoma

BACKGROUND: Teniposide (VM-26) has been widely used in the treatment of small cell lung cancer, malignant lymphoma, breast cancer, etc. However, there are few reports on VM-26 against oral cancers. The present study was designed to identify the effect of VM-26 against oral squamous cell carcinoma in vitro, and to provide evidence for the feasibility and effectiveness of VM-26 for application to the patients with oral cancer. METHODS: Human tongue squamous cell carcinoma cell line, Tca8113, was used. Cells were incubated with different concentrations of VM-26 for a variety of time span. Cisplatin (CDDP) was employed as a control reagent. MTT assay was used to assess the inhibitory rate of Tca8113 growth. Flow cytometer (FCM), transmission electronic microscope (TEM) and fluorescence staining were employed for determining the cell apoptotic rate. Cell cycle distribution of Tca8113 incubated with VM-26 was examined by flow cytometer assay. Statistic software (SAS 6.12, USA) was used for one-way ANOVA. RESULTS: The IC50 of VM-26 against Tca8113 cells was 0.35 mg/l and that of CDDP was 1.1 mg/l. The morphological changes of Tca8113 cells were observed with fluorescence microscope and TEM. Apoptotic morphological feature could be found in the nucleus. Apoptotic rate of Tca8113 cells incubated with 5.0 mg/l of VM-26 for 72 hours was 81.67% and cells waere arrested at S phase. However, when exposed to 0.15 mg/l of VM-26 for 72 hours, G2/M phase increased from 12.75% to 98.71%, while the apoptotic rate was 17.38%, which was lower than that exposed to 5.0 mg/l of VM-26. CONCLUSION: VM-26 could significantly induce apoptosis of oral squamous cell carcinoma and inhibit cell growth. There may be another pathway to induce apoptosis of oral squamous cell carcinoma cells except for G2/M phase arrest

SpOctA: A 3D Sparse Convolution Accelerator with Octree-Encoding-Based Map Search and Inherent Sparsity-Aware Processing

Point-cloud-based 3D perception has attracted great attention in various applications including robotics, autonomous driving and AR/VR. In particular, the 3D sparse convolution (SpConv) network has emerged as one of the most popular backbones due to its excellent performance. However, it poses severe challenges to real-time perception on general-purpose platforms, such as lengthy map search latency, high computation cost, and enormous memory footprint. In this paper, we propose SpOctA, a SpConv accelerator that enables high-speed and energy-efficient point cloud processing. SpOctA parallelizes the map search by utilizing algorithm-architecture co-optimization based on octree encoding, thereby achieving 8.8-21.2x search speedup. It also attenuates the heavy computational workload by exploiting inherent sparsity of each voxel, which eliminates computation redundancy and saves 44.4-79.1% processing latency. To optimize on-chip memory management, a SpConv-oriented non-uniform caching strategy is introduced to reduce external memory access energy by 57.6% on average. Implemented on a 40nm technology and extensively evaluated on representative benchmarks, SpOctA rivals the state-of-the-art SpConv accelerators by 1.1-6.9x speedup with 1.5-3.1x energy efficiency improvement.Comment: Accepted to ICCAD 202

Tertiary Regulation of Cascaded Run-of-the-River Hydropower in the Islanded Renewable Power System Considering Multi-Timescale Dynamics

To enable power supply in rural areas and to exploit clean energy, fully renewable power systems consisting of cascaded run-of-the-river hydropower and volatile energies such as pv and wind are built around the world. In islanded operation mode, the primary and secondary frequency control, i.e., hydro governors and automatic generation control (AGC), ensure the frequency stability. However, due to limited water storage capacity of run-of-the-river hydropower and river dynamics constraints, without coordination between the cascaded plants, the traditional AGC with fixed participation factors cannot fully exploit the adjustability of cascaded hydropower. When imbalances between the volatile energy and load occur, load shedding can be inevitable. To address this issue, this paper proposes a coordinated tertiary control approach by jointly considering power system dynamics and the river dynamics that couples the cascaded hydropower plants. The timescales of the power system and river dynamics are very different. To unify the multi-timescale dynamics to establish a model predictive controller that coordinates the cascaded plants, the relation between AGC parameters and turbine discharge over a time interval is approximated by a data-based second-order polynomial surrogate model. The cascaded plants are coordinated by optimising AGC participation factors in a receding-horizon manner, and load shedding is minimised. Simulation of a real-life system shows a significant improvement in the proposed method in terms of reducing load shedding.Comment: Submitted to IET Renewable Power Generation; 11 page

Effects of fertilizer application schemes and soil environmental factors on nitrous oxide emission fluxes in a rice-wheat cropping system, east China

Nitrous oxide (N2O) is a potent greenhouse gas (GHG) with agricultural soils representing its largest anthropogenic source. However, the mechanisms involved in the N2O emission and factors affecting N2O emission fluxes in response to various nitrogenous fertilizer applications remain uncertain. We conducted a four-year (2012–2015) field experiment to assess how fertilization scheme impacts N2O emissions from a rice-wheat cropping system in eastern China. The fertilizer treatments included Control (CK), Conventional fertilizer (CF), CF with shallow-irrigation (CF+SI), CF with deep-irrigation system (CF+DI), Optimized fertilizer (OF), OF with Urease inhibitor (OF+UI), OF with conservation tillage (OF+CT) and Slow-release fertilizer (SRF). N2O emissions were measured by a closed static chamber method. N2O emission fluxes ranged from 0.61 μg m-2 h-1 to 1707 μg m-2 h-1, indicating a significant impact of nitrogen fertilizer and cropping type on N2O emissions. The highest crop yields for wheat (3515–3667 kg ha-1) and rice (8633–8990 kg ha-1) were observed under the SRF and OF+UI treatments with significant reduction in N2O emissions by 16.94–21.20% and 5.55–7.93%, respectively. Our findings suggest that the SRF and OF+UI treatments can be effective in achieving maximum crop yield and lowering N2O emissions for the rice-wheat cropping system in eastern China

Identification of lipid droplet structure-like/resident proteins in Caenorhabditis elegans.

The lipid droplet (LD) is a cellular organelle that stores neutral lipids in cells and has been linked with metabolic disorders. Caenorhabditis elegans has many characteristics which make it an excellent animal model for studying LDs. However, unlike in mammalian cells, no LD structure-like/resident proteins have been identified in C. elegans, which has limited the utility of this model for the study of lipid storage and metabolism. Herein based on three lines of evidence, we identified that MDT-28 and DHS-3 previously identified in C. elegans LD proteome were two LD structure-like/resident proteins. First, MDT-28 and DHS-3 were found to be the two most abundant LD proteins in the worm. Second, the proteins were specifically localized to LDs and we identified the domains responsible for this targeting in both proteins. Third and most importantly, the depletion of MDT-28 induced LD clustering while DHS-3 deletion reduced triacylglycerol content (TAG). We further characterized the proteins finding that MDT-28 was ubiquitously expressed in the intestine, muscle, hypodermis, and embryos, whereas DHS-3 was expressed mainly in intestinal cells. Together, these two LD structure-like/resident proteins provide a basis for future mechanistic studies into the dynamics and functions of LDs in C. elegans

Transverse electric field–induced deformation of armchair single-walled carbon nanotube

The deformation of armchair single-walled carbon nanotube under transverse electric field has been investigated using density functional theory. The results show that the circular cross-sections of the nanotubes are deformed to elliptic ones, in which the tube diameter along the field direction is increased, whereas the diameter perpendicular to the field direction is reduced. The electronic structures of the deformed nanotubes were also studied. The ratio of the major diameter to the minor diameter of the elliptic cross-section was used to estimate the degree of the deformation. It is found that this ratio depends on the field strength and the tube diameter. However, the field direction has little role in the deformation

Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma

Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46−0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor β receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC

Immunogenicity and protective potential of chimeric virus-like particles containing SARS-CoV-2 spike and H5N1 matrix 1 proteins

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases