Formate and CO2 Enable Reductive Carboxylation of Imines: Synthesis of Unnatural α-Amino Acids.

Herein, a photocatalytic umpolung strategy for reductive carboxylation of imines for the synthesis of α-amino acids was disclosed. Carbon dioxide radical anion (CO2•-) generated from formate is the key single electron reductant in the reactions. An unprecedentedly broad substrate scope of imines with excellent reaction yields was obtained with carbon dioxide (CO2) and formate salt as carbon sources.

FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.

Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate-aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD.

Beam quality control technology for solid-state lasers based on thermal effects.

Thermal effects under high-power pumping significantly limit the laser beam quality. To address this, we developed an M2 simulation algorithm based on ray trajectory simulation and established a corresponding experimental platform. This approach optimized the M2 factor of pulsed lasers to 2.2 and output power of 25.9 W under a repetition rate of 10 kHz. The results revealed that under specific conditions, thermal effects, typically considered detrimental to beam quality, could significantly enhance it. Compared to other methods necessitating additional optical components, our strategy offers a streamlined and straightforward solution for beam quality control under high-power pumping conditions.

Identification of novel SCD1 inhibitor alleviates nonalcoholic fatty liver disease: critical role of liver-adipose axis.

Due to the complexity and incomplete understanding of the crosstalk between liver and adipose tissue, especially the processes of hepatic lipogenesis and adipogenic differentiation, there are currently no effective drugs for the treatment of nonalcoholic fatty liver disease (NAFLD). Stearoyl-coenzyme A desaturase 1 (SCD1), which is abundantly expressed in liver and adipose tissue, may mediate the cross-talk between liver and adipose tissue. Thus, it is essential to develop specific SCD1 inhibitors that target the liver-adipose axis. Herein, we identified a novel SCD1 inhibitor, E6446, through a high-throughput virtual screen. E6646 significantly inhibited adipogenic differentiation and hepatic lipogenesis via SCD1-ATF3 signaling. The SPR results showed that E6446 had a strong interaction ability with SCD1 (KD:4.61 µM). Additionally, E6646 significantly decreased hepatic steatosis, hepatic lipid droplet accumulation and insulin resistance in high-fat diet (HFD)-fed mice. Taken together, our findings not only suggest that E6446 can serve as a new, safe and highly effective anti-NAFLD agent for future clinical use but also provide a molecular basis for the future development of SCD1 inhibitors that inhibit both adipogenic differentiation and hepatic lipogenesis. Video Abstract.

Exploring the impact of fungal spores from agricultural environments on the mice lung microbiome and metabolic profile.

Exposure to particulate matter (PM) from agricultural environments has been extensively reported to cause respiratory health concerns in both animals and agricultural workers. Furthermore, PM from agricultural environments, containing fungal spores, has emerged as a significant threat to public health and the environment. Despite its potential toxicity, the impact of fungal spores present in PM from agricultural environments on the lung microbiome and metabolic profile is not well understood. To address this gap in knowledge, we developed a mice model of immunodeficiency using cyclophosphamide and subsequently exposed the mice to fungal spores via the trachea. By utilizing metabolomics techniques and 16 S rRNA sequencing, we conducted a comprehensive investigation into the alterations in the lung microbiome and metabolic profile of mice exposed to fungal spores. Our study uncovered significant modifications in both the lung microbiome and metabolic profile post-exposure to fungal spores. Additionally, fungal spore exposure elicited noticeable changes in α and ß diversity, with these microorganisms being closely associated with inflammatory factors. Employing non-targeted metabolomics analysis via GC-TOF-MS, a total of 215 metabolites were identified, among which 42 exhibited significant differences. These metabolites are linked to various metabolic pathways, with amino sugar and nucleotide sugar metabolism, as well as galactose metabolism, standing out as the most notable pathways. Cysteine and methionine metabolism, along with glycine, serine and threonine metabolism, emerged as particularly crucial pathways. Moreover, these metabolites demonstrated a strong correlation with inflammatory factors and exhibited significant associations with microbial production. Overall, our findings suggest that disruptions to the microbiome and metabolome may hold substantial relevance in the mechanism underlying fungal spore-induced lung damage in mice.

Microbiological characteristics of different tongue coatings in adults.

BACKGROUND: Tongue coating is an important health indicator in traditional Chinese medicine (TCM). The tongue coating microbiome can distinguish disease patients from healthy controls. To study the relationship between different types of tongue coatings and health, we analyzed the species composition of different types of tongue coatings and the co-occurrence relationships between microorganisms in Chinese adults. From June 2019 to October 2020, 158 adults from Hangzhou and Shaoxing City, Zhejiang Province, were enrolled. We classified the TCM tongue coatings into four different types: thin white tongue fur (TWF), thin yellow tongue fur (TYF), white greasy tongue fur (WGF), and yellow greasy tongue fur (YGF). Tongue coating specimens were collected and used for 16S rRNA gene sequencing using the Illumina MiSeq system. Wilcoxon rank-sum and permutational multivariate analysis of variance tests were used to analyze the data. The microbial networks in the four types of tongue coatings were inferred independently using sparse inverse covariance estimation for ecological association inference. RESULTS: The microbial composition was similar among the different tongue coatings; however, the abundance of microorganisms differed. TWF had a higher abundance of Fusobacterium periodonticum and Neisseria mucosa, the highest α-diversity, and a highly connected community (average degree = 3.59, average closeness centrality = 0.33). TYF had the lowest α-diversity, but the most species in the co-occurrence network diagram (number of nodes = 88). The platelet-to-lymphocyte ratio (PLR) was associated with tongue coating (P = 0.035), and the YGF and TYF groups had higher PLR values. In the co-occurrence network, Aggregatibacter segnis was the "driver species" of the TWF and TYF groups and correlated with C-reactive protein (P < 0.05). Streptococcus anginosus was the "driver species" in the YGF and TWF groups and was positively correlated with body mass index and weight (P < 0.05). CONCLUSION: Different tongue coatings have similar microbial compositions but different abundances of certain bacteria. The co-occurrence of microorganisms in the different tongue coatings also varies. The significance of different tongue coatings in TCM theory is consistent with the characteristics and roles of the corresponding tongue-coating microbes. This further supports considering tongue coating as a risk factor for disease.

Lipid metabolism gene-wide profile and survival signature of lung adenocarcinoma.

BACKGROUND: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. METHODS: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. RESULTS: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. CONCLUSIONS: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.

A Clinical Application Study of Nanostructured Substrates for the Detection of Circulating Tumor Cells.

BACKGROUND: Circulating tumor cell (CTC) isolation methods based on nanostructured substrates can be used to isolate tumor cells from peripheral blood. This study aimed to validate the clinical application of our method and determine the appropriate diagnostic critical value. METHODS: AFM was used to detect the surface roughness of nanostructured substrates. Cell lines and blood samples were used to verify CTC isolation methods. The ROC curve and AUC were used to evaluate the diagnostic value of CTC numbers. RESULTS: First, AFM, cell binding yields, and tumor cell detection rate from blood showed that NS has a potential for cell adsorption. Then, the CTC detection method was verified by using cell lines and blood samples. The number of CTCs in patients with cancers or metastases were significantly greater than those of patients without cancers. Then, the ROC curves and AUC showed that this method had a medium diagnostic value. CONCLUSIONS: Isolating CTCs based on nanostructured substrates was appropriate for the clinical diagnosis of tumors, and samples with more than 1.5 CTCs/1 mL blood could be identified as CTC-positive.

Cryptoporus volvatus polysaccharides attenuate LPS-induced expression of pro-inflammatory factors via the TLR2 signaling pathway in human alveolar epithelial cells.

CONTEXT: Cryptoporus volvatus (Peck) Hubb grows wild in China, and its fruiting bodies have been used traditionally to treat asthma and bronchitis. OBJECTIVES: This study evaluates the anti-inflammatory effect of Cryptoporus polysaccharides (CP) extracted from fruiting bodies of C. volvatus on lipopolysaccharide (LPS)-induced pro-inflammatory factors and the signaling pathways involved in human alveolar epithelial cells. MATERIALS AND METHODS: To evaluate the effects of CP on LPS-induced pro-inflammatory factors, A549 cells were pre-incubated with CP 1, 10, and 100 µg/ml for 1 h and then stimulated with LPS 10 µg/ml for 24 h. The expression of pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), Toll-like receptor 2 (TLR2), and phosphorylation of ERK1/2, p38, and NF-κB p65 were measured by q-PCR, ELISA, and western blotting. RESULTS: CP decreased LPS-induced mRNA expression of MCP-1, TNF-α, and IL-1ß (IC50 = 83.3, 85.2, and 91.6 µg/ml, respectively) and their correspondent protein expression (IC50 = 88.6, 76.4, and 81.6 µg/ml, respectively). Investigation of potential mechanisms indicated that CP 100 µg/ml reduced LPS-induced expression of TLR2 mRNA (66.9%, p < 0.01) and protein (63.2%, p < 0.01) that was a result of the decreased pro-inflammatory factors. LPS induction increased the expression of TLR2 and the phosphorylation of p38 and ERK1/2, NF-kB p65 concomitantly. CP 100 µg/ml inhibited the LPS-induced phosphorylation of the signaling proteins (p < 0.05). CONCLUSIONS: This suggests that CP pretreatment down-regulates LPS-mediated inflammation in lung epithelial cells. This study further confirmed that CP is a potential anti-inflammatory drug for the treatment of airway inflammatory diseases.

Pre-expanded thoracodorsal artery perforator-based flaps for repair of severe scarring in cervicofacial regions.

BACKGROUND: Reconstruction of cervicofacial scarring continues to present challenges for surgical treatment. Here we present our clinical experience in repairing cervicofacial scarring using pre-expanded thoracodorsal artery perforator flaps. METHODS: From January 2007 to December 2012, 15 patients were treated for severe cervicofacial scarring. In the first surgical stage, expanders were implanted subcutaneously in the zone nourished by thoracodorsal artery perforators. The expansion generally took 3 to 6 months. In the second surgical stage, the cervicofacial cicatricial contracture was released and the secondary defect was covered with local flaps. The remaining wound was covered by the free thoracodorsal artery perforator expanded flap, which was anastomosed to the facial vascular bundle. The donor site was closed directly in all the patients. RESULTS: The postoperative follow-up time ranged from 1 to 5 years. The deformities were corrected, all flaps survived completely and none were bulky. The maximum length of the flaps was 32 cm (mean, 22.4 ± 4.2 cm), and the maximum width was 17 cm (mean, 14.4 ± 2.2 cm). All patients exhibited recovery of neck movement, and there was no recurrence of neck contracture. CONCLUSION: The pre-expanded thoracodorsal artery perforator flap is an ideal method for reconstruction of severe cervicofacial cicatricial contracture.

Silencing PCMT1 enhances the sensitivity of breast cancer cells to paclitaxel through the PI3K/Akt/STMN1 pathway.

This study aimed to investigate whether silencing Protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) expression can enhance the sensitivity of breast cancer cells to paclitaxel and its possible mechanism. Tumor tissues and adjacent histologically normal tissues were collected from patients with breast cancer admitted to our hospital. Human normal breast epithelial cells MCF10A, human breast cancer cells MCF-7, and paclitaxel-resistant breast cancer cells MCF-7/PR were purchased. MCF-7/PR cells were further grouped into negative control (NC) group, si-PCMT1 group (transfected with si-PCMT1), 740Y-P group (treated with 740Y-P, an activator of phosphatidylinositol 3-kinase (PI3K)/ v-Akt Murine Thymoma Viral Oncogene (AKT) signaling pathway), and si-PCMT1 + 740Y-P group (transfected with si-PCMT1 and then treated with 740Y-P). The expression level of PCMT1 in tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was used to detect the protein expression level of PCMT1 in tissues and cells as well as the protein level of p-PI3K, PI3K, p-Akt, Akt, and Stathmin1 (STMN1) in cells. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assays were used to determine cell viability, scratch assay was used to assess the migration ability of cells, and Transwell assay was used to assess the invasion ability of cells. The expression of PCMT1 was remarkably up-regulated in breast cancer tissues and MCF-7/PR cells. Silencing PCMT1 expression significantly inhibited the proliferation, migration, and invasion of MCF-7/PR cells, and alleviated the resistance of cancer cells to paclitaxel. Additionally, silencing PCMT1 expression also inhibited the activation of PI3K/Akt/STMN1 pathway in MCF-7/PR cells, while activating PI3K/Akt/STMN1 pathway significantly reversed the effect of silencing PCMT1 expression on MCF-7/PR cells. PCMT1 is highly expressed in breast cancer tissues and MCF-7/PR cells, and silencing PCMT1 expression can not only inhibit the development of breast cancer but also enhance paclitaxel sensitivity. Its mechanism of action may be achieved by inhibiting PI3K/Akt/STMN1 signaling.

The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review.

Fatty acid metabolism is a complex biochemical process, including the production, breakdown and application of fatty acids. Not only is it an important component of lipid metabolism, fatty acid metabolism is also connected to the energy metabolism pathways of cells and plays a vital role in maintaining the energy balance of organisms. Diacylglycerol-O-acyltransferase 1 (DGAT1) and Diacylglycerol-O-acyltransferase 2 (DGAT2) are key components in regulating lipid metabolism, which provide energy for cell proliferation and growth. Recent studies have shown that DGAT1 and DGAT2 influence tumor progression through fatty acid metabolism in cancer. Although DGAT1 and DGAT2 have similar names, they differ significantly in various aspects and play distinct roles in individual tumors. A comparative analysis of the physiological roles of these enzymes and their differential expressions in different types of tumors will enhance our understanding of their unique characteristics. This article summarizes the characteristics of tumor fatty acid metabolism and explains how DGAT1 and DGAT2 specifically promote tumor progression. In addition, this review discusses the potential of lipid-lowering drugs in tumor treatment, providing a new perspective on targeting fatty acid metabolism to inhibit tumor progression in the future, while emphasizing the importance of DGAT1 and DGAT2 as potential targets for tumor treatment.

Microglial Ffar4 deficiency promotes cognitive impairment in the context of metabolic syndrome.

Metabolic syndrome (MetS) is closely associated with an increased risk of dementia and cognitive impairment, and a complex interaction of genetic and environmental dietary factors may be implicated. Free fatty acid receptor 4 (Ffar4) may bridge the genetic and dietary aspects of MetS development. However, the role of Ffar4 in MetS-related cognitive dysfunction is unclear. In this study, we found that Ffar4 expression is down-regulated in MetS mice and MetS patients with cognitive impairment. Conventional and microglial conditional knockout of Ffar4 exacerbated high-fat diet (HFD)-induced cognitive dysfunction and anxiety, whereas microglial Ffar4 overexpression improved HFD-induced cognitive dysfunction and anxiety. Mechanistically, we found that microglial Ffar4 regulated microglial activation through type I interferon signaling. Microglial depletion and NF-κB inhibition partially reversed cognitive dysfunction and anxiety in microglia-specific Ffar4 knockout MetS mice. Together, these findings uncover a previously unappreciated role of Ffar4 in negatively regulating the NF-κB-IFN-ß signaling and provide an attractive therapeutic target for delaying MetS-associated cognitive decline.

Lactobacillus rhamnosus GG Promotes Recovery of the Colon Barrier in Septic Mice through Accelerating ISCs Regeneration.

Disruption of the intestinal barrier is both the cause and result of sepsis. The proliferation and differentiation of intestinal stem cells (ISCs) promote the regenerative nature of intestinal epithelial cells, repairing the injured intestinal mucosal barrier; however, it is uncertain whether the recovery effects mediated by the ISCs are related to the gut microbiota. This research found that the survival rate of septic mice was improved with a Lactobacillus rhamnosus GG (LGG) treatment. Furthermore, an increased proliferation and decreased apoptosis in colon epithelial cells were observed in the LGG-treated septic mice. In vitro, we found that a LGG supernatant was effective in maintaining the colonoid morphology and proliferation under the damage of TNF-α. Both in the mice colon and the colonoid, the LGG-induced barrier repair process was accompanied by an increased expression of Lgr5+ and lysozyme+ cells. This may be attributed to the upregulation of the IL-17, retinol metabolism, NF-kappa B and the MAPK signaling pathways, among which, Tnfaip3 and Nfkbia could be used as two potential biomarkers for LGG in intestinal inflammation therapy. In conclusion, our finding suggests that LGG protects a sepsis-injured intestinal barrier by promoting ISCs regeneration, highlighting the protective mechanism of oral probiotic consumption in sepsis.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Pulmonary microbiota signatures adjacent to adenocarcinoma, squamous cell carcinoma and benign lesion.

Introduction: The occurrence and progression of lung cancer are influenced by pulmonary microbiota, yet the relationship between changes in the pulmonary microbiota and lung cancer remains unclear. Methods: To investigate the correlation between pulmonary microbiota and the signature of lung lesions, we analyzed the microbial composition at sites adjacent to the stage 1 adenocarcinoma, squamous carcinoma and benign lesion tissues in 49 patients by using 16S ribosomal RNA gene sequencing. We then conducted Linear discriminant analysis, receiver operating characteristic (ROC) curve analysis and PICRUSt prediction based on 16S sequencing results. Results: Overall, the microbiota composition at sites close to lung lesions showed significant differences between different lesion types. Based on the results of LEfSe analysis, Ralstonia, Acinetobacter and Microbacterium are the dominant genera of lung adenocarcinoma (LUAD), lung squamous carcinoma (LUSC) and benign lesions (BENL), respectively. Furthermore, we determined the diagnostic value of the abundance ratio of Ralstonia to Acinetobacter in adenocarcinoma patients through ROC curve analysis. The PICRUSt analysis revealed 15 remarkably different metabolic pathways in these lesion types. In LUAD patients, the increase of the pathway associated with xenobiotic biodegradation may be due to the continuous proliferation of microbe with degradation ability of xenobiotics, which implied that LUAD patients are often exposed to harmful environment. Discussion: The abundance of Ralstonia was related to the development of lung cancer. By measuring the abundance of microbiota in diseased tissues, we can distinguish between different types of lesions. The differences in pulmonary microbiota between lesion types are significant in understanding the occurrence and development of lung lesions.

Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus-induced acute lung injury.

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

CUL3 and COPS5 Related to the Ubiquitin-Proteasome Pathway Are Potential Genes for Muscle Atrophy in Mice.

Sarcopenia is a condition that reduces muscle mass and exercise capacity. Muscle atrophy is a common manifestation of sarcopenia and can increase morbidity and mortality in specific patient populations. The aim of this study was to identify novel prognostic biomarkers for muscle atrophy and associated pathway analysis using bioinformatics methods. The samples were first divided into different age groups and different muscle type groups, respectively, and each of these samples was analyzed for differences to obtain two groups of differentially expressed genes (DEGs). The two groups of DEGs were intersected using Venn diagrams to obtain 1,630 overlapping genes, and enrichment analysis was performed to observe the Gene Ontology (GO) functional terms of overlapping genes and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Subsequently, WGCNA (weighted gene coexpression network analysis) was used to find gene modules associated with both the age and muscle type to obtain the lightgreen module. The genes in the key modules were analyzed using PPI, and the top five genes were obtained using the MCC (maximum correntropy criterion) algorithm. Finally, CUL3 and COPS5 were obtained by comparing gene expression levels and analyzing the respective KEGG pathways using gene set enrichment analysis (GSEA). In conclusion, we identified that CUL3 and COPS5 may be novel prognostic biomarkers in muscle atrophy based on bioinformatics analysis. CUL3 and COPS5 are associated with the ubiquitin-proteasome pathway.

circCCT3 Enhances Invasion and Epithelial-Mesenchymal Transition (EMT) of Non-Small-Cell Lung Cancer (NSCLC) via the miR-107/Wnt/FGF7 Axis.

Background: CircRNAs play a role in a variety of biological processes, including tumorigenesis. circCCT3 has been shown to regulate cancer initiation and progression. Unfortunately, whether circCCT3 is involved in non-small-cell lung cancer (NSCLC) metastasis remains unclear. Methods: Our study utilized RT-qPCR to examine gene expression levels. A transwell assay was used to measure invasion ability of cells. Starbase software and TargetScan software were used to predict target genes. Results: circCCT3 knockdown attenuated invasion and epithelial-mesenchymal transition (EMT) of A549 and Calu-1 cells. miR-107 mimics could rescue circCCT3-induced invasion and EMT. Next, miR-107 mimics and circCCT3 knockdown suppressed Wnt3a and FGF7 expression. An miR-107 inhibitor promoted Wnt3a and FGF7 expressions. Finally, FGF7 greatly restored miR-107-inhibited invasion and EMT of A549 cells. Conclusion: Here, we reveal a molecular mechanism circCCT3/miR-107/Wnt/FGF7 responsible for NSCLC metastasis.