Image_3_Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.tif

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.</p

Table_1_Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.xlsx

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.</p

Image_2_Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.tif

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.</p

Engineering Soluble Human Paraoxonase 2 for Quorum Quenching

Many pathogenic bacteria utilize quorum sensing (QS) systems to regulate the expression of their virulence genes and promote the formation of biofilm, which renders pathogens with extreme resistance to conventional antibiotic treatments. As a novel approach for attenuating antibiotic resistance and in turn fighting chronic infections, enzymatic inactivation of QS signaling molecules, such as N-acyl homoserine lactones (AHLs), holds great promises. Instead of using bacterial lactonases that can evoke immune response when administered, we focus on the human paraoxonase 2 (huPON2). However, insolubility when heterologously overexpressed hinders its application as anti-infection therapeutics. In this study, huPON2 was engineered for soluble expression with minimal introduction of foreign sequences. On the basis of structure modeling, degenerate linkers were exploited for the removal of hydrophobic helices of huPON2 without disrupting its folding structure and thus retaining its enzymatic function. High soluble expression levels were achieved with a yield of 76 mg of fully human PON2 variants per liter of culture media. Particularly, two clones, D2 and E3, showed significant quorum quenching (QQ) bioactivities and effectively impeded <i>Pseudomonas aeruginosa</i> swimming and swarming motilities, signs of an early stage of biofilm formation. In addition, by correlating QQ with luminescence signal readouts, quantitative analysis of QQ toward natural or non-natural AHL-regulator combinations suggested that D2 and E3 exhibited strong lactone hydrolysis activities toward five AHLs of different side chain lengths and modifications widely utilized by a variety of biomedically important pathogens

Image_1_Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.tif

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.</p

GO analysis showed that the most enriched and activated functional gene group in the differential genes of BLEL includes genes related to signaling pathways mediated by the complement system.

<p>GO analysis showed that the most enriched and activated functional gene group in the differential genes of BLEL includes genes related to signaling pathways mediated by the complement system.</p

Exploring the Native Chemical Ligation Concept for Highly Stereospecific Glycosylation Reactions

Various <i>O</i>-alkyl glycosides were obtained in a highly stereospecific manner with retention of configuration at the anomeric center. Our method has customized native chemical ligation concept for glycoconjugates synthesis, utilizing a meticulously controlled activating system. To explain the origin of stereoselective preference, an S_Ni mechanism was proposed and corroborated by computational calculations

3 genes that were upregulated as identified by microarray data, were subjected to RT-PCR analysis for confirmation purposes.

<p>The results of differences in gene expression from microarray and RT-PCR were found to be consistent.</p

Differentially expressed genes of the complement System in BLEL.

<p>Differentially expressed genes of the complement System in BLEL.</p

Both C3c (A) and C1q (C) expressions were positive in the BLEL samples (black arrows), while negative in the control group (B and D).

<p>Both C3c (A) and C1q (C) expressions were positive in the BLEL samples (black arrows), while negative in the control group (B and D).</p