The role of tumor-associated macrophages in glioma cohort: through both traditional RNA sequencing and single cell RNA sequencing

Gliomas are the leading cause in more than 50% of malignant brain tumor cases. Prognoses, recurrences, and mortality are usually poor for gliomas that have malignant features. In gliomas, there are four grades, with grade IV gliomas known as glioblastomas (GBM). Currently, the primary methods employed for glioma treatment include surgical removal, followed by chemotherapy after the operation, and targeted therapy. However, the outcomes of these treatments are unsatisfactory. Gliomas have a high number of tumor-associated macrophages (TAM), which consist of brain microglia and macrophages, making them the predominant cell group in the tumor microenvironment (TME). The glioma cohort was analyzed using single-cell RNA sequencing to quantify the genes related to TAMs in this study. Furthermore, the ssGSEA analysis was utilized to assess the TAM-associated score in the glioma group. In the glioma cohort, we have successfully developed a prognostic model consisting of 12 genes, which is derived from the TAM-associated genes. The glioma cohort demonstrated the predictive significance of the TAM-based risk model through survival analysis and time-dependent ROC curve. Furthermore, the correlation analysis revealed the significance of the TAM-based risk model in the application of immunotherapy for individuals diagnosed with GBM. Ultimately, the additional examination unveiled the prognostic significance of PTX3 in the glioma group, establishing it as the utmost valuable prognostic indicator in patients with GBM. The PCR assay revealed the PTX3 is significantly up-regulated in GBM cohort. Additionally, the assessment of cell growth further confirms the involvement of PTX3 in the GBM group. The analysis of cell proliferation showed that the increased expression of PTX3 enhanced the ability of glioma cells to proliferate. The prognosis of glioblastomas and glioma is influenced by the proliferation of tumor-associated macrophages

Replacing Traditional Plastics with Biodegradable Plastics:Impact on Carbon Emissions

In recent years, a great deal of attention has been focused on the environmental impact of plastics, including the carbon emissions related to plastics, which has promoted the application of biodegradable plastics. Countries worldwide have shown high interest in replacing traditional plastics with biodegradable plastics. However, no systematic comparison has been conducted on the carbon emissions of biodegradable versus traditional plastic products. This study evaluates the carbon emissions of traditional and biodegradable plastic products (BPPs) over four stages and briefly discusses environmental and economic perspectives. Four scenarios—namely, the traditional method, chemical recycling, industrial composting, and anaerobic digestion—are considered for the disposal of waste biodegradable plastic product (WBBPs). The analysis takes China as a case study. The results show that the carbon emissions of 1000 traditional plastic products (plastic bags, lunch boxes, cups, etc.) were 52.09–150.36 carbon emissions equivalent of per kilogram (kg CO2eq), with the stage of plastic production contributing 50.71%–50.77%. In comparison, 1000 similar BPPs topped out at 21.06–56.86 kg CO2eq, approximately 13.53%–62.19% lower than traditional plastic products. The difference was mainly at the stages of plastic production and waste disposal, and the BPPs showed significant carbon reduction potential at the raw material acquisition stage. Waste disposal plays an important role in environmental impact, and composting and anaerobic digestion are considered to be preferable disposal methods for WBBPs. However, the high cost of biodegradable plastics is a challenge for their widespread use. This study has important reference significance for the sustainable development of the biodegradable plastics industry.</p

Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Large Eddy Simulation of Cavitation Jets from an Organ-Pipe Nozzle: The Influence of Cavitation on the Vortex Coherent Structure

High-speed water jets are widely used in deep mining and the in-depth study of jet characteristics helps to improve drilling efficiency. Three-dimensional Large Eddy Simulation is used to simulate turbulent flows generated by an organ-pipe nozzle. The simulation is validated with existing experimental data and is focused on the evolution and interaction of cavitation bubbles and vortices. Dynamic mode decomposition is performed to extract structural information about the different motion modes and their stability. Results show that the dominant fluid frequency is positively correlated with inlet pressure while unrelated to the divergence angle. Meanwhile, jets’ oscillation is amplified by a large divergence angle, which facilitates the occurrence of cavitation. Results about the flow field outside of an organ-pipe nozzle advance the understanding of the basic mechanism of cavitation jets

High Concentrations of Uric Acid Inhibit Angiogenesis via Regulation of the Krüppel-Like Factor 2-Vascular Endothelial Growth Factor-A Axis by miR-92a

Background: Angiogenesis is a critical component of many pathological conditions, and microRNAs (miRNAs) are indispensable in angiogenesis. It is unclear whether miRNAs regulate angiogenesis in the presence of high concentrations of uric acid (HUA), and the underlying mechanisms remain unknown. Methods and Results: It was found that HUA inhibited the angiogenic ability of endothelial cells. miRNA expression profiling was conducted using microarray assays in HUA-stimulated endothelial cells. Eighteen differentially expressed miRNAs were subjected to bioinformatic analyses. The results indicated that miR-92a was negatively regulated and was closely related to angiogenesis. Furthermore, the effects of miR-92a on HUA-stimulated endothelial cell angiogenesis and the underlying mechanisms were investigated in dual-luciferase reporter assays, electrophoretic mobility shift assays, immunoblot assays, and tube formation assays. It was determined that Kruppell-like factor 2 (KLF2) is a target gene of miR-92a, and KLF2 binds the vascular endothelial growth factor-A (VEGFA) promoter to inhibit its expression. miR-92a and VEGFA overexpression or KLF2 downregulation alleviates the HUA-mediated inhibition of angiogenesis in endothelial cells in vitro. Conclusions: This study reported that there is a novel pathway regulating angiogenesis under HUA conditions. In the presence of HUA, miR-92a downregulation increased KLF2 expression, subsequently inhibiting VEGFA, which resulted in decreased angiogenesis. Thus, this study reports a possible mechanism for cardiovascular injury caused by hyperuricemia and suggests that the miR-92a-KLF2-VEGFA axis may be a target for hyperuricemia treatment.Chinese National Natural Sciences Foundation [31170810, 81470949, 81102673]; Beijing NOVA Program [Z121107002512078]; Major State Basic Research Development Program of China [2013CB530800]SCI(E)[email protected]+7

Replacing Traditional Plastics with Biodegradable Plastics: Impact on Carbon Emissions

In recent years, a great deal of attention has been focused on the environmental impact of plastics, including the carbon emissions related to plastics, which has promoted the application of biodegradable plastics. Countries worldwide have shown high interest in replacing traditional plastics with biodegradable plastics. However, no systematic comparison has been conducted on the carbon emissions of biodegradable versus traditional plastic products. This study evaluates the carbon emissions of traditional and biodegradable plastic products (BPPs) over four stages and briefly discusses environmental and economic perspectives. Four scenarios—namely, the traditional method, chemical recycling, industrial composting, and anaerobic digestion—are considered for the disposal of waste biodegradable plastic product (WBBPs). The analysis takes China as a case study. The results show that the carbon emissions of 1000 traditional plastic products (plastic bags, lunch boxes, cups, etc.) were 52.09–150.36 carbon emissions equivalent of per kilogram (kg CO2eq), with the stage of plastic production contributing 50.71%–50.77%. In comparison, 1000 similar BPPs topped out at 21.06–56.86 kg CO2eq, approximately 13.53%–62.19% lower than traditional plastic products. The difference was mainly at the stages of plastic production and waste disposal, and the BPPs showed significant carbon reduction potential at the raw material acquisition stage. Waste disposal plays an important role in environmental impact, and composting and anaerobic digestion are considered to be preferable disposal methods for WBBPs. However, the high cost of biodegradable plastics is a challenge for their widespread use. This study has important reference significance for the sustainable development of the biodegradable plastics industry.ISSN:2095-809