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Supplementary Table from Tumor Microenvironment Acidity Triggers Lipid Accumulation in Liver Cancer via SCD1 Activation

Supplementary Figure from Tumor Microenvironment Acidity Triggers Lipid Accumulation in Liver Cancer via SCD1 Activation

With the development of additive manufacturing, the advantages of this type implant devices in the treatment of acetabular defects and reconstruction are becoming more and more prominent. The number of registration and declaration of such products is increasing day by day. According to the relevant requirements of the National Medical Products Administration for registration and application documents, combined with the characteristics of acetabular reconstruction implant products made of additive manufacturing, this study analyzes and summarizes the relevant requirements on raw material control, product performance research, product manufacturing, clinical evaluation, et al. We should pay more attention to in the registration and application materials submitted by the applicant. Provide opinions and suggestions for the next registration applicant to standardize product RD and registration application documents, in order to help them optimize product RD process, improve product quality and registration application efficiency.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients’ survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

The ‘plainification of materials’ has been conceptualized to promote the sustainable development of materials. This perspective, for the first time in the field of biomaterials, proposes and defines ‘plain metallic biomaterials (PMBs)’ with demonstrated research and application case studies of pure titanium with high strength and toughness, and biodegradable, fine-grained and high-purity magnesium. Then, after discussing the features, benefits and opportunities of PMBs, the challenges are analyzed from both technical and regulatory aspects. Regulatory perspectives on PMB-based medical devices are also provided for the benefit of future research, development and commercialization.

Exploring efficient control strategies for heterogeneously congested urban networks remains a big research challenge. The theory of macroscopic fundamental diagram (MFD) provides a new perspective for network-wide congestion control decisions. This paper proposes a coordinated perimeter control strategy for multiregion heterogeneous networks based on optimized transfer flows. First, a two-layer network partitioning method is presented to capture spatial heterogeneity dynamics of urban networks. For this partition, traffic flow equilibrium model based on MFD and multiagent based hierarchical traffic management scheme are built. Then, an improved multinomial logit model is developed for deriving optimized transfer flows among multiple congested regions. A coordinated perimeter control strategy using model predictive control is further proposed, which is aimed at tracking desired accumulations of each congested region. As a case study, the proposed control strategy is applied to the downtown network of Jinan, China, using simulation analysis. The results demonstrate that it can achieve balanced network flow distribution and increased mobility.

This study assessed the effects of different electric current densities on the calcification and photosynthetic physiology of a massive, colonial stony coral species. Coral survivorship, calcification rate, and photosynthetic parameters (zooxanthellae density and chlorophyll fluorescence) were measured to determine the physiological and photosynthetic performance of Galaxea fascicularis after exposure to different electric current densities. After 60 days of treatment, survival of G. fascicularis was higher at low electric current density (10 mA m−2) than in the control and at high electric current density (100 mA m−2). Electric current did not alter zooxanthellae densities, but did enhance the photosynthetic processes (e.g. maximum electron transport rates (rETRm), and maximum quantum yield (Fv/Fm)) within 45 days. Coral calcification rate increased in response to low electric current density up to 30 days, but the effects of the electric current were not significant after a longer period of treatment. Overall, our results indicated that mineral accretion technology with appropriate electric current density conditions was somewhat helpful in enhancing coral growth, and thus this technique may be used in the restoration and management of massive stony coral reefs.

Background Fibronectin type III domain containing 3B (FNDC3B) acts as an oncogene in various cancers, and abnormal expression of FNDC3B has been found in colorectal cancer (CRC). Our study aimed to illustrate the role of FNDC3B in CRC development. Methods Through RT-qPCR and western blotting assays, the mRNA and protein expressions of target genes were measured. CCK-8 and MTT methods were used to detect cell proliferation. Invasion ability was determined using Transwell assay. TargetScan platform and luciferase reporter gene assay were performed to predict and validate the bindings between FNDC3B and miR-125a-5p or miR-217. Besides, the expression correlation was measured by Pearson's Correlation analysis. Results We found that FNDC3B was significantly upregulated in CRC tissues and tumor cell lines, and high expression of FNDC3B predicted a poor survival outcome. The bindings between FNDC3B and miR-125a-5p and miR-217 were respectively at the motifs of CUCAGGG and AUGCAGU. MiR-125a-5p and miR-217 were downregulated in CRC tissues, and both were negatively correlated with FNDC3B expression. Subsequently, the downregulated miR-125a-5p and miR-217 were confirmed as contributors FNDC3B upregulation in CRC. A loss-of-function assay demonstrated that FNDC3B knockdown inhibited the proliferation of CRC cells, while FNDC3B overexpression promoted the proliferation and invasion of tumor cells. Besides, we validated that PI3K/mTOR signaling was involved in the regulation of FNDC3B on the proliferation and invasion of CRC cells. Conclusion Generally, our findings demonstrated that FNDC3B facilitated cell proliferation and invasion via PI3K/mTOR signaling, and further promoted CRC progression. The novel miR-125a-5p/FNDC3B and miR-217/FNDC3B axes might be new targets for CRC prognosis and therapy.

The effects of a simulated climate change scenario, i.e., increased ultraviolet radiation (UVR) and dissolved organic carbon (DOC), on the growth and photosynthesis of tropical coastal phytoplankton were evaluated in Sanya Bay, northern South China Sea, in summer. Microcosm experiments were conducted at two contrasting stations (Stns S1 and S2) with three different UVR treatments and two DOC addition treatments. Our results showed that natural sunlight UVR or increased UV-B did not affect phytoplankton biomass and primary production. However, increased UV-B significantly decreased the proportion of picophytoplankton and the efficiency of carbon fixation at Stn S2. DOC enhancement caused negative effects on primary production under natural sunlight UVR only at Stn S1. Interactive effects of UVR and DOC addition on phytoplankton biomass and primary production were detected at Stn S1, due to the negative effects of DOC being eliminated under the increased UV-B condition. The lack of interactive effects at Stn S2 were likely due to the differences with Stn S1 in terms of light acclimation and biological interaction. In summary, this future climate change scenario will probably not affect the photosynthetic CO2 fixation and biomass of natural phytoplankton in Sanya Bay.

Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src‐associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC., Here, we report that Sam68, an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents.

Coronavirus disease 2019 pandemic continues globally with a growing number of infections, but there are currently no effective antibody drugs against the virus. In addition, 90% amino acid sequence identity between the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV S proteins attracts us to examine S2-targeted cross-neutralizing antibodies that are not yet well defined. We therefore immunized RenMab mice with the full-length S protein and constructed a high-throughput antibody discovery method based on single-cell sequencing technology to isolate SARS-CoV-2 S-targeted neutralizing antibodies and cross-neutralizing antibodies against the S2 region of SARS-CoV-2/SARS-CoV S. Diversity of antibody sequences in RenMab mice and consistency in B-cell immune responses between RenMab mice and humans enabled screening of fully human virus-neutralizing antibodies. From all the frequency >1 paired clonotypes obtained from single-cell V(D)J sequencing, 215 antibodies with binding affinities were identified and primarily bound S2. However, only two receptor-binding domain-targeted clonotypes had neutralizing activity against SARS-CoV-2. Moreover, 5' single-cell RNA sequencing indicated that these sorted splenic B cells are mainly plasmablasts, germinal center (GC)-dependent memory B-cells and GC B-cells. Among them, plasmablasts and GC-dependent memory B-cells were considered the most significant possibility of producing virus-specific antibodies. Altogether, using a high-throughput single cell-based antibody discovery approach, our study highlighted the challenges of developing S2-binding neutralizing antibodies against SARS-CoV-2 and provided a novel direction for the enrichment of antigen-specific B-cells.

Tissue development deformity or tissue defect is a major clinical challenge. Tissue engineering technology provides a promising solution to these problems. Among them, functional biomaterials with regenerative abilities are one of the development trends. Polypeptide is a small molecule that can be used to modify tissue engineering materials. However, the function of a single polypeptide molecule is limited and insufficient to construct comprehensive microenvironment for tissue regeneration. Fusion peptides combining two or more polypeptide molecules with different functions were expected to achieve multiple efficacies in vivo, providing a novel solution for clinical tissue regeneration engineering applications. This paper reviews the construction methods, degradation process, and biological activities of fusion peptides, and presents recent global research progress and prospects concerning fusion peptides. It provides a reference helping to guide the future exploration and development of fusion peptide-based functional biomaterials for tissue engineering.

Acidification is recognized as the predominant characteristic of the tumor microenvironment (TME) and contributes to tumor progression. However, the mechanism of extracellular acidic TME directly influences intercellular pathologic responses remains unclear. Meanwhile, acidic TME is mainly ascribed to aberrant metabolism of lipids and glucose, but whether and how acidity affects metabolic reprogramming, especially for lipid metabolism, is still unknown. We found that lipid was significantly accumulated in liver cancer cells when exposed to acidic TME. Moreover, proteomic analysis showed that differentially expressed proteins were mainly clustered into fatty acid pathways. Subsequently, we found that acidification increased the expression of SCD1 by activating PI3K/AKT signaling pathway. Interestingly, we found that SCD1 directly bound to PPARα in the acidic TME, which vanished after 2-day reverse incubation in pH 7.4 medium, implying extracellular acidosis might influence intercellular function by mediating the binding affinity between SCD1 and PPARα under different pH gradients. In summary, our data revealed that acidosis could significantly trigger fatty acid synthesis to promote liver tumorigenesis by upregulating SCD1 in a PI3K/AKT activation dependent manner and simultaneously promote SCD1 binding to PPARα. Our study not only provides direct mechanistic evidence to support the vital role of acidosis in lipid metabolic reprogramming, but also provides novel insights for determining the binding affinity of functional proteins as a molecular mechanism to better understand the role of the acidic TME in tumor development. Implications: The acidic TME contributes to lipid accumulation in liver cancer by activating the PI3K/AKT signaling pathway and promoting SCD1–PPARα binding.

Network-wide traffic control strategies (e.g. perimeter control and route guidance) in urban networks have recently been mainly studied to relieve or postpone congestion based on the theory of macroscopic fundamental diagram (MFD). Nevertheless, these studies are mostly applied to the statically partitioned networks or the dynamic networks that fail to fully consider traffic state prediction, conflicting with strongly spatiotemporal variability of traffic congestion or objective of active traffic management (ATM). This paper proposes a methodology to dynamically identify critical congestion warning areas from heterogeneous urban road networks, which aids to design efficient perimeter control approaches. In the methodology, a dynamic directed weighted network is built on the base of the link connectivity and the real-time traffic loads, and a link travel time prediction method based on Kalman filter is developed to calibrate directed weight values and undirected input values for links. With the undirected link input information, a dynamic congestion warning community detection method which consists of three consecutive steps is developed. Firstly, it could capture emergence of new congestion areas based on the definition of congestion seed intersection. Secondly, expansion and regression of each congested area could be achieved with the objectives of spatial compactness and traffic condition homogeneity. Thirdly, a two-level merging algorithm of adjacent different congestion areas is designed utilizing modularity model in community detection of complex networks. The proposed methodology is validated using ground truth data from downtown network of Jinan City in China. The results show that the proposed algorithms can efficiently track congestion evolutionary processes and effectively detect congestion warning areas from the test real network.

Recent studies have indicated that various corals might have different degrees of resistance to elevated CO2 levels. However, the underlying molecular mechanism accounting for these differences is still poorly understood. In this study, RNA-seq data were analyzed to identify differentially expressed genes in two coral species (Acropora austera and Acropora cerealis) in response to high CO2 levels. The calcification rates were higher in high CO2 treatment than the control in A. austera, but was not significantly different in A. cerealis. A KEGG database search revealed that in both coral species, most Ca2+ transporters were present in the calcium signaling pathway, which could be important in the CO2 regulation of coral calcification. The gene expression levels of many CO2 and HCO3- transporters were not affected by elevated CO2. Nevertheless, high CO2 levels did have an effect on the expression of certain Ca2+ transporters. The upregulation of Ca2+ transporters likely explained the higher resistance of A. austera to high CO2 than A. cerealis.

H- and Nb-doped ZnO (HNZO) thin films were fabricated on glass substrates with radio frequency magnetron sputtering. The effect of the flow rate of H2 has been investigated by analyzing the structural, optical, and electrical properties. The incorporation of H during the deposition of Nb-incorporated ZnO films significantly improved their crystallinity, conductivity, and transmittance. The crystallites of the HNZO films were preferentially oriented in the c-axis direction; the films possess high transmittance (approximately 85%) in the visible and near-infrared regions (400 to 1400 nm). The lowest room-temperature resistivity of the HNZO films was measured as 1.28 × 10−3 Ω cm. Such optical and electrical properties along with the remarkable chemical stability of the HNZO films make them a promising candidate for applications in solar cells.

The annual sea surface temperature increased at a rate of 0.038 to 0.074 °C/year in recent decade, and pH decreased at a rate of 0.012–0.014/year in two coastal waters of the South China Sea. Therefore, a culture experiment was conducted to study the effects of acidification and warming on coral calcification rates. The calcification of three coral species were significantly reduced during the exposure to elevated CO2, while other three coral species were not significantly affected. The reef coral Pocillopora damicornis was resistant to high CO2, but was not able to survive during the exposure to 33 °C in our culture experiments. Our findings suggested that some corals might not survive in tropical areas if coral could not adapt to warming rapidly, and subtropical coastal waters with temperature of

Bile acids (BAs), the most important components of bile, attribute predominately to maintain metabolic homeostasis. In hepatocellular carcinoma (HCC) patients, the BAs homeostasis was seriously disturbed, especially in those patients with alcohol-intake history. However, whether alcohol consumption could promote HCC progression via influencing BAs homeostasis and the precise mechanism underlying are still unclear. In our study, by collecting HCC specimens from both alcohol-drinkers (n = 15) and non-alcohol drinkers (n = 22), we found that compared to non-alcohol intake HCC patients, BAs homeostasis was disturbed in HCC patients who drank alcohol. Furthermore, ethanol treatment was also found to promote HCC progression by markedly activating oncogenes (RAS, MYC, MET, and HER2), while remarkably suppressing tumor suppressor genes (BRCA2 and APC). We evaluated 14 key functional genes that maintain the homeostasis of BAs and found that either in alcohol-intake HCC patients (n = 15), or in ethanol-treated mice, BSEP, rate-limiting transporter governing excreting BAs from liver into bile duct, was remarkably decreased when exposed to alcohol. Moreover, by screening for changes in the epigenetic landscape of liver cancer cells exposed to alcohol, we strikingly found that histone methyltransferases (RBBP-5, Suv39h1, ASH2L, and SET7/9) were increased, and KMT3B, KMT4, and KMT7 gene expression was also elevated, while histone demethyltransferases (JARID1a, JARID1b, JARID1c) were decreased. In summary, we found that alcohol could trigger BAs disequilibrium to initiate and promote HCC progression. Our study provided a novel and supplementary mechanism to determine the important role of alcohol-intake in HCC development regarding from the perspective of BAs homeostasis.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF

The development of society requires high-quality talents, which propels colleges and universities to cultivate graduates with both theoretical and practical abilities. As an applied undergraduate university, Beijing City University has always attached importance to cultivating students' practical ability based on theoretical teaching. In “Project Planning and Control”, a module for the major of project management, the task-driven method is used for practical training. The college aims to improve students' ability to apply the theory through practical training scenarios, real-life training tasks, assessments and other key steps. In order to test the effect of practical training, SPSS statistical software is used to perform paired sample T test and correlation analysis on the usual scores and final scores. The analysis results show that the design of practical training is reasonable, achieving good results.