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Lactic acid, once considered as an endpoint or a waste metabolite of glycolysis, has emerged as a major regulator of cancer development, maintenance, and progression. However, studies about lactic acid metabolism-related genes (LRGs) in lung adenocarcinoma (LUAD) remain unclear. Two distinct molecular subtypes were identified on basis of 24 LRGs and found the significant enrichment of subtype A in metabolism-related pathways and had better overall survival (OS). Subsequently, a prognostic signature based on 5 OS-related LRGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. Then, a highly accurate nomogram was cosntructed to improve the clinical application of the LRG_score. By further analyzing the LRG_score, higher immune score and lower stromal score were found in the low LRG_score group, which presented a better prognosis. Patients with low LRG_score also exhibited lower somatic mutation rate, tumor mutation burden (TMB), and cancer stem cell (CSC) index. Three more independent cohorts (GSE126044: anti-PD-1, GSE135222: anti-PD-1, and IMvigor210: anti-PD-L1) were analyzed, and the results showed that patients in the low LRG_score category were more responsive to anti-PD-1/PD-L1 medication and had longer survival times. It was also determined that gefitinib, etoposide, erlotinib, and gemcitabine were more sensitive to the low LRG_score group. Finally, we validated the stability and reliability of LRG_score in cell lines, clinical tissue samples and HPA databases. Overall, the LRG_score may improve prognostic information and provide directions for current research on drug treatment strategies for LUAD patients.

Spherical MCM-41 with various copper and iron loadings was prepared by surfactant directed co-condensation method. The obtained samples were characterized with respect to their structure (X-ray diffraction, XRD), texture (N2 sorption), morphology (scanning electron microscopy, SEM), chemical composition (inductively coupled plasma optical emission spectrometry, ICP-OES), surface acidity (temperature programmed desorption of ammonia, NH3-TPD), form, and aggregation of iron and copper species (diffuse reflectance UV-Vis spectroscopy, UV-Vis DRS) as well as their reducibility (temperature programmed reduction with hydrogen, H2-TPR). The spherical MCM-41 samples modified with transition metals were tested as catalysts of selective catalytic reduction of NO with ammonia (NH3-SCR). Copper containing catalysts presented high catalytic activity at low-temperature NH3-SCR with a very high selectivity to nitrogen, which is desired reaction products. Similar results were obtained for iron containing catalysts, however in this case the loadings and forms of iron incorporated into silica samples very strongly influenced catalytic performance of the studied samples. The efficiency of the NH3-SCR process at higher temperatures was significantly limited by the side reaction of direct ammonia oxidation. The reactivity of ammonia molecules chemisorbed on the catalysts surface in NO reduction (NH3-SCR) and their selective oxidation (NH3-SCO) was verified by temperature-programmed surface reactions.

Background Cultivated tea is one of the most important economic and ecological trees distributed worldwide. Cultivated tea suffer from long-term targeted selection of traits and overexploitation of habitats by human beings, which may have changed its genetic structure. The chloroplast is an organelle with a conserved cyclic genomic structure, and it can help us better understand the evolutionary relationship of Camellia plants. Results We conducted comparative and evolutionary analyses on cultivated tea and wild tea, and we detected the evolutionary characteristics of cultivated tea. The chloroplast genome sizes of cultivated tea were slightly different, ranging from 157,025 to 157,100 bp. In addition, the cultivated species were more conserved than the wild species, in terms of the genome length, gene number, gene arrangement and GC content. However, comparing Camellia sinensis var. sinensis and Camellia sinensis var. assamica with their cultivars, the IR length variation was approximately 20 bp and 30 bp, respectively. The nucleotide diversity of 14 sequences in cultivated tea was higher than that in wild tea. Detailed analysis on the genomic variation and evolution of Camellia sinensis var. sinensis cultivars revealed 67 single nucleotide polymorphisms (SNPs), 46 insertions/deletions (indels), and 16 protein coding genes with nucleotide substitutions, while Camellia sinensis var. assamica cultivars revealed 4 indels. In cultivated tea, the most variable gene was ycf1 . The largest number of nucleotide substitutions, five amino acids exhibited site-specific selection, and a 9 bp sequence insertion were found in the Camellia sinensis var. sinensis cultivars. In addition, phylogenetic relationship in the ycf1 tree suggested that the ycf1 gene has diverged in cultivated tea. Because C. sinensis var. sinensis and its cultivated species were not tightly clustered. Conclusions The cultivated species were more conserved than the wild species in terms of architecture and linear sequence order. The variation of the chloroplast genome in cultivated tea was mainly manifested in the nucleotide polymorphisms and sequence insertions. These results provided evidence regarding the influence of human activities on tea.

The tea plant is a vital strategic forest resource in China. Dark tea produced from its leaves is an indispensable health-promoting product in western China due to its unique lipid-lowering function. Eurotium cristatum is the dominant strain in Fuzhuan brick tea (a variety of Anhua dark tea) and could produce many functional components, including lovastatin, a lipid-lowering compound. In this study, the lovastatin yield of dark tea was improved by breeding Eurotium cristatum using the protoplast fusion method. The experiments were carried out by inducing a fusion between inactivated Eurotium cristatum JH1205 and Monascus CICC5031. Among the 92 fusants screened the HPLC method, four strains (A4, A36, A54, and A76) with higher lovastatin production (more than three times as high) were obtained. The A76 strain had the highest lovastatin yield, which was 23.93 μg/mL. The location of the tea forest strongly influenced the lovastatin yield of loose dark tea. The strain bred in this study improved the lovastatin yield of loose dark tea by more than three times when compared to wild Eurotium cristatum. These results are promising for the development of tea forest resources.

Background Acute pancreatitis is a rare but serious complication for pregnant women. Early identification of severity of acute pancreatitis in pregnancy (APIP) is of great significance to the treatment. The aim of this study was to investigate the risk factors and develop a novel model for predicting the prognosis of APIP patients. Methods A retrospective study was conducted from December 2005 to June 2024. Univariate and multivariate analyses were used to identify the risk factors of APIP. LASSO regression and logistic regression were employed to develop prognosis model of APIP patients and nomogram was plotted. The performance of the predictive model was evaluated using the receiver operating characteristic curve, calibration curve and decision curve analysis. Results A total of 45 patients with APIP were enrolled in this study. Univariate and multivariate logistic regression analysis determined that albumin (OR = 0.72, 95%CI: 0.51–0.90, P  = 0.019) and blood urea nitrogen (OR = 1.45, 95%CI: 1.11–2.14, P  = 0.021) measured within 24 h of admission were independent risk factors of severity in APIP. Additionally, a prognostic model consisting of albumin and blood urea nitrogen was developed based on LASSO and logistic regression models. Nomogram was established and visualized. The nomogram achieved a higher AUC value of 0.920 than BISAP score (AUC = 0.875) and SIRS score (AUC = 0.728). Besides, The AUC of nomogram to predict ICU admission in APIP patients was 0.819. Calibration curve indicated that the prediction model has good calibration performance, while decision curve confirmed its clinical utility. Conclusion This study developed a novel and simple nomogram to predict the severity and ICU admission of APIP patients, which is of great value in guiding APIP management.

Forest plants contain abundant natural products, providing a valuable resource for obtaining compounds with various functional activities, such as antimicrobial, lipid-lowering, and immunoregulatory activities. The development of efficient tools for rapidly screening functional natural products from forest plants is essential for human health. In this study, we constructed some transgenic strains (Escherichia coli) containing Ahy1-1 riboswitches that respond to cyclic di-guanylate (c-di-GMP), serving as a novel bacteriostatic target. The Ahy1-1 riboswitches contained the LacZ gene (encoding β-galactosidase) and c-di-GMP aptamer in order to monitor β-galactosidase activity due to changes in c-di-GMP. After co-incubating with extracts from fresh orange peel, fresh tea leaves, and Fuzhuan brick tea, the orange peel exhibited a significant inhibition of c-di-GMP generation. The extract of tea leaves had a minor influence on the synthesis of c-di-GMP, whereas Fuzhuan brick tea, which is fermented by various microorganisms, inhibited the production of c-di-GMP. Our constructed transgenic strains could be used to screen for antibacterial agents from forest plants. Beyond antibacterial agents, other functional compounds from forest plants could be selected by designing diverse riboswitches.

The prevention and prediction of sudden cardiac death (SCD) present persistent challenges, prompting exploration into common genetic variations for potential insights. T-box 5 (TBX5), a critical cardiac transcription factor, plays a pivotal role in cardiovascular development and function. This study systematically examined variants within the 500-bp region downstream of the TBX5 gene, focusing on their potential impact on susceptibility to SCD associated with coronary artery disease (SCD-CAD) in four different Chinese Han populations. In a comprehensive case-control analysis, we explored the association between rs11278315 and SCD-CAD susceptibility using a cohort of 553 controls and 201 SCD-CAD cases. Dual luciferase reporter assays and genotype-phenotype correlation studies using human cardiac tissue samples as well as integrated in silicon analysis were applied to explore the underlining mechanism. Binary logistic regression results underscored a significantly reduced risk of SCD-CAD in individuals harboring the deletion allele (odds ratio = 0.70, 95% CI [0.55-0.88], = 0.0019). Consistent with the lower transcriptional activity of the deletion allele observed in dual luciferase reporter assays, genotype-phenotype correlation studies on human cardiac tissue samples affirmed lower expression levels associated with the deletion allele at both mRNA and protein levels. Furthermore, our investigation revealed intriguing insights into the role of rs11278315 in TBX5 alternative splicing, which may contribute to alterations in its ultimate functional effects, as suggested by sQTL analysis. Gene ontology analysis and functional annotation further underscored the potential involvement of TBX5 in alternative splicing and cardiac-related transcriptional regulation. In summary, our current dataset points to a plausible correlation between rs11278315 and susceptibility to SCD-CAD, emphasizing the potential of rs11278315 as a genetic risk marker for aiding in molecular diagnosis and risk stratification of SCD-CAD.

Background RNA methylation is a potential target for cancer therapy, while anoikis, a form of programmed cell death, is linked to cancer metastasis. However, the prognostic and immune significance of RNA methylation- and anoikis-related genes in colorectal cancer (CRC) remains unknown. Methods Transcriptomic and clinicopathological data for CRC were obtained from TCGA and the GEO databases. A novel signature was constructed based on RNA methylation- and anoikis-related genes using univariate and multivariate Cox regression as well as LASSO Cox regression methods. CRC patients were stratified into low- and high-risk groups based on this signature. Differences in prognosis, immune infiltration, and drug sensitivity between two groups were analyzed. Finally, immunohistochemistry, western blot, and RT-qPCR were employed to validate the expression of the key gene SERPINE1 in CRC tissues and cells, as well as the effect of FTO on its expression. Results We identified 79 differentially expressed RNA methylation-associated anoikis-related genes (RMRARGs) in both cancerous and normal tissues. A signature composed of 9 key genes (BID, FASN, PLK1, CDKN3, MYC, EPHA2, SERPINE1, CD36, PDK4) was established. Kaplan–Meier analysis revealed a poorer prognosis in the high-risk group. Compared to the other three published models, this signature demonstrated superior predictive performance based on the ROC curve analysis. Functional analyses highlighted differences in drug sensitivities and signaling pathways between risk groups. Furthermore, immune analysis results showed that risk score was associated with some immune cells and immune checkpoints. Immunohistochemistry showed high SERPINE1 expression in CRC tissues, with FTO expression positively correlated with SERPINE1. Furthermore, RT-qPCR and western blot indicated FTO knockdown markedly downregulated SERPINE1 levels. Conclusion Our findings underscore the prognostic value of this signature in CRC patients and its utility in assessing immune status. Additionally, the m6A demethylase FTO regulates the expression of the anoikis-related gene SERPINE1.

Aspergillus cristatus are the dominantly present microorganisms in dark tea. The whole mitochondrial genome sequence of A. cristatus was sequenced and reported in this study. The mitochondrial genome in A. cristatushas a full length of 77,649 bp, which is reported to be the longest among the mitochondrial genomes of Aspergillus species. The basesincluding A (34.14％), T (37.64％), C (15.61％) and G (12.61％) are found in their genome. A total of 42 genes (15 protein-coding genes, lrRNA/srRNA and 25 tRNAs) are encoded by the mitochondrial genome of this fungus. Phylogenetic analysis showed a closest relationship betweenA. pseudoglaucusand the taxonomic status of A. cristatus.

Penicillium citrinum is a common polluting microorganism in dark tea production. Our study was performed to report the complete mitochondrial genome of P. citrinum. The mitochondrial genome of P. citrinum was a circular DNA molecule of 27,537 bp in length, encoding 42 genes as follows: 15 PCGs, two rRNAs, 24 tRNAs, and an independent ORF. A (36.14%), T (37.06%), C (11.83%), and G (14.98%) was composed of genomic bases. In addition, phylogenetic analysis showed that Penicillium sp. exhibited a closest relationship with the taxonomic status of P. citrinum.