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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.

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.

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.

Ethnopharmacological relevance Herb-derived anti-tumor agents, such as paclitaxel and vincristine, exert significant but varied effectivenesses towards different cancer types. Similarly, Centipeda minima (CM) is a well-known traditional Chinese medicine that has been used to treat rhinitis, relieve pain and reduce swelling, and recently found to exert overwhelming anti-tumor effects against breast cancer, colon cancer, and nasopharyngeal carcinoma with different response rates. However, what is the optimizing cancer model that benefits most from CM, and what is the specific target underlying still require more exclusive and profound investigations. Aims of the study This study aimed to explore the dominant tumor model and specific target of CM by integrative pharmacology and biological experiments. Materials and methods The most predominant and specific cancer types that are sensitive to CM were screened and identified based on a combination network pharmacology and bioinformatics analysis. Compound-target network and protein-protein interaction of CM-related cancer targets were carried out to determine the most abundant active compound. Simultaneously, the priority target responsible for CM-related anti-tumor efficacy was further validated by molecular docking and in vitro experiments. Results In total, approximately 42% (8/19) of the targets were enriched in prostate cancer (p = 1.25E-09), suggesting prostate cancer would be the most sensitive tumor response to CM-related efficacy. Furthermore, we found that arnicolide D (ARD), the most abundant and representative active compound of CM, could directly bind to Src with binding energy of -7.3 kcal/mol, implying Src would be the priority target responsible for CM-related anti-tumor efficacy. Meanwhile, the results were further validated by solvent-induced protein precipitation (SIP) assay. In addition, PCR and WB results also revealed that either CM or ARD could not influence the gene expression of Src, while significantly decreased its protein expression instead, which further suggested that ARD might markedly shortene the Src protein half-life to promote Src protein degradation, thereby achieving significant anti-prostate cancer efficacy. Conclusion Our findings not only suggest CM as a promising Src-targeting candidate for prostate cancer treatment, but also bring up a strategy for understanding the personalization of herbal medicines by using integrative pharmacology.