Search

Introduction: Kidney renal clear cell carcinoma (KIRC), as a main type of malignant kidney cancers, has a poor prognosis. Epithelial-mesenchymal transformation (EMT) exerts indispensable role in tumor progression and metastasis, including in KIRC. This study aimed to mine more EMT related details and build prognostic signature for KIRC.Methods: The KIRC scRNA-seq data and bulk data were downloaded from GEO and TCGA databases, respectively. The cell composition in KIRC was calculated using CIBERSORT. Univariate Cox regression analysis and LASSO Cox regression analysis were combined to determine the prognostic genes. Gene set variation analysis and cell-cell communication analysis were conducted to obtain more functional information. Additionally, functional analyses were conducted to determine the biological roles of si-LGALS1 in vitro.Results: We totally identified 2,249 significant differentially expressed genes (DEGs) in KIRC samples, meanwhile a significant distinct expression pattern was found in KIRC, involving Epithelial Mesenchymal Transition pathway. Among all cell types, significantly higher proportion of epithelial cells were observed in KIRC, and 289 DEGs were identified in epithelial cells. After cross analysis of all DEGs and 970 EMT related genes, SPARC, TMSB10, LGALS1, and VEGFA were optimal to build prognostic model. Our EMT related showed good predictive performance in KIRC. Remarkably, si-LGALS1 could inhibit migration and invasion ability of KIRC cells, which might be involved in suppressing EMT process.Conclusion: A novel powerful EMT related prognostic signature was built for KIRC patients, based on SPARC, TMSB10, LGALS1, and VEGFA. Of which, si-LGALS1 could inhibit migration and invasion ability of KIRC cells, which might be involved in suppressing EMT process.

IntroductionLipidomics elucidates the roles of lipids in both physiological and pathological processes, intersecting with many diseases and cellular functions. The maintenance of lipid homeostasis, essential for cell health, significantly influences the survival, maturation, and functionality of sperm during fertilization. While capacitation and the acrosome reaction, key processes before fertilization, involve substantial lipidomic alterations, a comprehensive understanding of the changes in human spermatozoa's lipidomic profiles during these processes remains unknown. This study aims to explicate global lipidomic changes during capacitation and the acrosome reaction in human sperm, employing an untargeted lipidomic strategy using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).MethodsTwelve semen specimens, exceeding the WHO reference values for semen parameters, were collected. After discontinuous density gradient separation, sperm concentration was adjusted to 2 x 106 cells/ml and divided into three groups: uncapacitated, capacitated, and acrosome-reacted. UPLC-MS analysis was performed after lipid extraction from these groups. Spectral peak alignment and statistical analysis, using unsupervised principal component analysis (PCA), bidirectional orthogonal partial least squares discriminant analysis (O2PLS-DA) analysis, and supervised partial least-squares-latent structure discriminate analysis (PLS-DA), were employed to identify the most discriminative lipids.ResultsThe 1176 lipid peaks overlapped across the twelve individuals in the uncapacitated, capacitated, and acrosome-reacted groups: 1180 peaks between the uncapacitated and capacitated groups, 1184 peaks between the uncapacitated and acrosome-reacted groups, and 1178 peaks between the capacitated and acrosome-reacted groups. The count of overlapping peaks varied among individuals, ranging from 739 to 963 across sperm samples. Moreover, 137 lipids had VIP values > 1.0 and twenty-two lipids had VIP > 1.5, based on the O2PLS-DA model. Furthermore, the identified twelve lipids encompassed increases in PI 44:10, LPS 20:4, LPA 20:5, and LPE 20:4, and decreases in 16-phenyl-tetranor-PGE2, PC 40:6, PS 35:4, PA 29:1, 20-carboxy-LTB4, and 2-oxo-4-methylthio-butanoic acid.DiscussionThis study has been the first time to investigate the lipidomics profiles associated with acrosome reaction and capacitation in human sperm, utilizing UPLC-MS in conjunction with multivariate data analysis. These findings corroborate earlier discoveries on lipids during the acrosome reaction and unveil new metabolites. Furthermore, this research highlights the effective utility of UPLC-MS-based lipidomics for exploring diverse physiological states in sperm. This study offers novel insights into lipidomic changes associated with capacitation and the acrosome reaction in human sperm, which are closely related to male reproduction.

Primary colon squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. Moreover, there is no treatment guideline for this disease. Proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal adenocarcinoma is refractory to immune monotherapy. Although the combination of immunotherapy with chemotherapy in pMMR/MSS colorectal cancer (CRC) is currently under investigation, the clinical activity of this approach in colorectal SCC remains unknown. In this article, we report the case of a pMMR/MSS CRC patient with ascending colon SCC who had high programmed cell death–ligand 1 (PD-L1) expression and the a missense mutation in codon 600 of the B-Raf proto-oncogene (BRAF V600E) mutation. The patient exhibited a significant response to the combination of immunotherapy and chemotherapy. After eight cycles of treatment with the combination of sintilimab and mFOLFOX6 (oxaliplatin, fluorouracil, and leucovorin), computed tomography–guided microwave ablation of the liver metastasis was performed. The patient achieved excellent durable response and continues to experience a good quality of life. The present case indicates that programmed cell death 1 blockade combined with chemotherapy may be an effective therapy for patients with pMMR/MSS colon SCC and high PD-L1 expression. Furthermore, PD-L1 expression may be a biomarker for immunotherapy in patients with colorectal SCC.

Single-atom catalysis is a research Frontier and has attracted extensive interests in catalysis. Significant progresses have been carried out in the synthesis and characterization of metal single-atom catalysts (SACs). However, the stability and catalytic reactivity of metal SAC at elevated temperatures are not well documented because single atoms sinter at elevated temperatures. Therefore, the development of stable and reactive SAC at high temperatures remains a formidable challenge. In this perspective, we summarize recent efforts on the preparation of the thermally-stable SACs synthesized at elevated temperature via the reverse-Ostwald ripening mechanism, including the approaches of atom trapping and vapor-phase self-assembly. The reducibility of lattice oxygen, the loading upper limit and the location of the metal single atom are discussed, combining experiments with simulations. In addition, we demonstrate that the coordination structure of the metal single atom can be tailored to address the relationship of structure and performances of the metal SAC in reactions. We expect that this perspective can provide some insights to guide the study for the rational design of thermally-stable and active single atom catalysts, which are especially suitable for high-temperature reactions.

The thermocatalytic conversion of hexose into valuable chemicals such as methyl lactate under mild conditions is very appealing. Here, we report that Mo, Mg co-modified Sn-β catalyst can effectively catalyze the transformation of glucose and fructose into alkyl lactate at moderate temperatures. A maximum yield of around 35% of methyl lactate was achieved from the conversion of glucose in methanol at 100°C over Sn-β catalyst modified with 3 wt% Mo and 0.5 wt% Mg. However, up to 82.8% yield of ethyl lactate was obtained in the case of fructose in ethanol upon the same catalytic condition, suggesting a significant solvent effect. The Mo species plays a key role to enable the retro-aldol condensation of fructose, in which the competing side reactions are significantly suppressed with the assistance of neighboring Mg species probably through a synergetic effect of Lewis acid-base.

Epithelial cells are held together by tight and adherent junctions, which are destroyed by the activation of epithelial-to-mesenchymal transition (EMT). The PLEKHA7-PDZD11 complex has been reported to be important for epithelial cell adhesion and connecting tissues. However, there is no research regarding the expression and role of PDZD11 in liver hepatocellular carcinoma (LIHC) progression. Here, we analyzed PDZD11 mRNA expression and its clinical results in LIHC patient RNA sequencing data based on different open databases. Furthermore, we examined differences in PDZD11 expression in LIHC tissues and cell lines using western blotting and real-time qPCR. These results are the first to report that the mRNA and protein levels of PDZD11 are significantly overexpressed in LIHC. Moreover, high expression of PDZD11 was correlated with poor overall survival in patients with LIHC. Gene regulatory network analysis suggested that PDZD11 is mainly involved in copper ion homeostasis, proteasome, and oxidative phosphorylation pathways. Interestingly, we found that PDZD11 levels were positively correlated with the abundance of immune infiltrates. In particular, higher infiltration levels of CD4+ T cells and macrophage subsets significantly affected LIHC patient prognosis. Taken together, these results demonstrate that PDZD11 could be a potential diagnostic and prognostic biomarker in LIHC.