Search Results (44)

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) and ROS1 (ROS proto-oncogene 1) rearrangements, BRAF (B-Raf proto-oncogene serine/threonine kinase) mutations, MET (mesenchymal–epithelial transition factor) alterations, KRAS (Kirsten rat sarcoma) mutations, HER2 (human epidermal growth factor receptor 2) alterations and emerging NTRK (neurotrophic receptor tyrosine kinase) fusions and AXL-related pathways. Methods: A total of 48 patients with NSCLC was analyzed, including 22 women and 26 men (mean age 70 years, range 44–86). Tumor specimens were classified histologically as adenocarcinomas (n = 81%) or squamous cell carcinomas (n = 19%). Smoking history, PD-L1 (programmed death-ligand 1) expression, and genetic alterations were assessed. NGS (Next-generation sequencing) identified genomic variants, which were classified according to ACMG (American College of Medical Genetics and Genomics) guidelines. Results: The cohort consisted of 29 former smokers, 13 current smokers, and 5 non-smokers (12%), with a mean smoking burden of 33 pack years. PD-L1 TPS (tumor proportion score) was ≥50% in 10 patients, ≥1–<50% in 22, and <1% in 15 patients. In total, 120 genomic variants were detected (allele frequency ≥ 5%). Of these, 52 (43%) were classified as likely pathogenic or pathogenic, 48 (40%) as variants of unknown significance, and 20 (17%) as benign or likely benign. The most frequently altered genes were TP53 (tumor protein p53) (31%), KRAS and EGFR (15% each), and STK11 (serine/threonine kinase 11) (12%). Adenocarcinomas accounted for 89% of all alterations, with TP53 (21%) and KRAS (15%) being most common, while squamous cell carcinomas predominantly harbored TP53 (38%) and MET (15%) mutations. In patients with PD-L1 TPS ≥ 50%, KRAS mutations were enriched (50%), particularly KRAS G12C and G12D, with frequent co-occurrence of TP53 mutations (20%). No pathogenic EGFR mutations were detected in this subgroup. Conclusions: Comprehensive genomic profiling in NSCLC revealed a high prevalence of clinically relevant mutations, with TP53, KRAS and EGFR as the dominant drivers. The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients. Full article

Straw returning is a critical practice with profound strategic importance for sustainable agricultural development. However, within a comprehensive soil health evaluation framework, research analyzing the impact of tobacco straw returning on soil ecosystem health from the perspectives of microbial taxa and functional genes remains insufficient. To investigate the effects of tobacco straw returning on virulence factor genes (VFGs), methane-cycling genes (MCGs), nitrogen-cycling genes (NCGs), carbohydrate-active enzyme genes (CAZyGs), antibiotic resistance genes (ARGs), and their host microorganisms in soil, this study collected soil samples from a long-term tobacco-rice rotation field with continuous tobacco straw incorporation in Shaowu City, Fujian Province. Metagenomic high-throughput sequencing was performed on the samples. The results demonstrated that long-term tobacco straw returning influenced the diversity of soil VFGs, MCGs, NCGs, CAZyGs, ARGs, and their host microorganisms, with richness significantly increasing compared to the CK treatment (p < 0.05). In the microbially mediated methane cycle, long-term tobacco straw returning resulted in a significant decrease in the abundance of the key methanogenesis gene mttB and the methanogenic archaeon Methanosarcina, along with a reduced mtaB/pmoA functional gene abundance ratio compared to CK. This suggests enhanced CH₄ oxidation in the tobacco-rice rotation field under straw returning. Notably, the abundance of plant pathogens increased significantly under tobacco straw returning. Furthermore, a significantly higher norB/nosZ functional gene abundance ratio was observed, indicating a reduced capacity of soil microorganisms to convert N₂O in the tobacco-rice rotation field under straw amendment. Based on the observation that the full-rate tobacco straw returning treatment (JT2) resulted in the lowest abundances of functional genes prkC, stkP, mttB, and the highest abundances of nirK, norB, malZ, and bglX, it can be concluded that shifts in soil physicochemical properties and energy substrates drove a transition in microbial metabolic strategies. This transition is characterized by a decreased pathogenic potential of soil bacteria, alongside an enhanced potential for microbial denitrification and cellulose degradation. Non-parametric analysis of matrix correlations revealed that soil organic carbon, dissolved organic carbon, alkaline-hydrolyzable nitrogen, available phosphorus, and available potassium were significantly correlated with the composition of soil functional groups (p < 0.05). In conclusion, long-term tobacco straw returning may increase the risk of soil-borne diseases in tobacco-rice rotation systems while potentially elevating N₂O and reducing CH₄ greenhouse gas emission rates. Analysis of functional gene abundance changes identified the full-rate tobacco straw returning treatment as the most effective among all treatments. Full article

Background/Objectives: Breast cancer represents a diverse group of malignancies and continues to rank among the leading causes of cancer-related deaths in women. Altered Hippo pathway signaling has been increasingly recognized as a contributor to tumor growth, therapeutic resistance, and metastatic spread. This study aimed to identify miRNAs targeting Hippo pathway-related genes that are consistently dysregulated across all five breast cancer subtypes. Methods: The study cohort included patients representing five breast cancer subtypes: 130 luminal A, 96 HER2-positive luminal B, 100 HER2-negative luminal B, 36 non-luminal HER2-positive, and 43 triple-negative breast cancer (TNBC). Tumor samples were collected during surgery, along with adjacent healthy tissue that served as controls. Expression of Hippo-related genes was analyzed using mRNA microarrays and validated with reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein levels were assessed via enzyme-linked immunosorbent assay (ELISA), while miRNA expression profiling was performed with miRNA microarrays. Potential mRNA targets were predicted using the miRDB database. Results: We identified consistent downregulation of STK4, RASSF6, and FGF1, alongside overexpression of BIRC5 and SERPINE1. miRNA analysis revealed that STK4 is potentially regulated by miR-522-3p, SERPINE1 by miR-199b-5p and miR-30a-3p, whereas RASSF6, FGF1, and BIRC5 appeared to be predominantly regulated at the transcriptional level. These alterations reflect both the suppression of upstream Hippo activation and activation of downstream oncogenic effectors across all subtypes. Conclusions: Our findings reveal a conserved Hippo dysregulation program in breast cancer, highlighting subtype-independent Hippo-related genes and their miRNA regulators as potential universal biomarkers and therapeutic targets, complementing subtype-specific treatment strategies. Full article

Lignocellulosic biomass may play a major role in the production of biofuels, bioplastics, sugar, paper, and various other industrial products. In addition, it is a key trait in plants due to its contribution to lodging resistance. Fiber also shows a significant negative correlation with most yield traits and all sugar traits. As the most harvested crop globally by tonnage, sugarcane is an important resource for both sugar and bioenergy production. In this study, a panel of sugarcane clones was utilized to investigate the fiber content. This panel included 17 core parental lines derived from 11 countries involved in sugarcane cultivation and breeding. It represented the genetic base of commercial sugarcane breeding programs in China and other countries. The objective of this research was to identify molecular markers and candidate genes associated with fiber content in sugarcane using genome-wide association studies (GWASs). By integrating 5,964,084 high-quality single-nucleotide polymorphisms (SNPs) with phenotypic data collected across five different environments, a total of 69 SNPs spanning 41 quantitative trait loci (QTLs) were identified. Based on functional annotations and genomic positions, these QTLs contained 52 candidate genes. These candidate genes encoded the ultraviolet-B receptor (UVR8), leucine-rich repeat receptor-like kinases (LRR-RLKs), serine/threonine kinases (STKs), cellulose synthase (CESA), vegetative cell wall protein glycoproteins1 (gp1), F-box protein, MYB transcription factor, and so on. These genes could directly or indirectly influence the fiber content in sugarcane. Furthermore, according to previous studies, among these candidate genes, five located in four QTL regions were proposed to be the most critical. They included Sspon.02G0041160-2C, encoding CESA; Sspon.03G0039010-1C and Sspon.03G0039030-1C, both encoding gp1; Sspon.06G0023090-1B, encoding an F-box protein; and Sspon.07G0019440-2C, encoding a MYB transcription factor. The genetic basis of the fiber content was explored using elite breeding lines and their derivatives from the Chinese sugarcane breeding program. These candidate genes represent promising targets for future functional studies and may contribute to the development of different types of sugarcane varieties with correspondingly suitable fiber content through marker-assisted selection. Full article

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings. Full article

Flowers, serving as the reproductive structures of angiosperms, perform an integral role in plant biology and are fundamental to understanding plant evolution and taxonomy. The growth and organogenesis of flowers are driven by numerous factors, such as external environmental conditions and internal physiological processes, resulting in diverse traits across species or even within the same species. Among these factors, genes play a central role, governing the entire developmental process. The regulation of floral genesis by these genes has become a significant focus of research. In the AE model of floral development, the five structural whorls (calyx, corolla, stamens, pistils, and ovules) are controlled by five groups of genes: A, B, C, D, and E. These genes interact to give rise to a complex control system that governs the floral organsgenesis. The activation or suppression of specific gene categories results in structural modifications to floral organs, with variations observed across different species. The present article examines the regulatory roles of key genes, including genes within the MADS-box and AP2/ERF gene clusters, such as AP1, AP2, AP3, AG, STK, SHP, SEP, PI, and AGL6, as well as other genes, like NAP, SPL, TGA, PAN, and WOX, in shaping floral organ genesis. In addition, it analyzes the molecular-level effects of these genes on floral organ formation. The findings offer a deeper understanding of the genetic governance of floral organ genesis across plant species. Full article

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, has emerged as a new threat to wheat production and quality in North China. Genetic enhancement of wheat resistance to FCR remains the most effective approach for disease control. In this study, we phenotyped 435 Chinese wheat cultivars through FCR inoculation at the seedling stage in a greenhouse. Our findings revealed that only approximately 10.8% of the wheat germplasms displayed moderate or high resistance to FCR. A genome-wide association study (GWAS) using high-density 660K SNP led to the discovery of a novel quantitative trait locus on the long arm of chromosome 3B, designated as Qfcr.hebau-3BL. A total of 12 significantly associated SNPs were closely clustered within a 1.05 Mb physical interval. SNP-based molecular markers were developed to facilitate the practical application of Qfcr.hebau-3BL. Among the five candidate FCR resistance genes within the Qfcr.hebau-3BL, we focused on TraesCS3B02G307700, which encodes a protein kinase, due to its expression pattern. Functional validation revealed two transcripts, TaSTK1.1 and TaSTK1.2, with opposing roles in plant resistance to fungal disease. These findings provide insights into the genetic basis of FCR resistance in wheat and offer valuable resources for breeding resistant varieties. Full article

The global rise in antibiotic resistance in bacteria poses a major challenge in treating infectious diseases. Polymyxins (e.g., polymyxin B and colistin) are last-resort antibiotics against resistant Gram-negative bacteria, but the effectiveness of polymyxins is decreasing due to widespread resistance among clinical isolates. The aim of this literature review was to decipher the evolving mechanisms of resistance to polymyxins among pathogens of clinical significance. We deciphered the molecular determinants of polymyxin resistance, including distinct intrinsic molecular pathways of resistance as well as evolutionary characteristics of mobile colistin resistance. Among clinical isolates, Acinetobacter stains represent a diversified evolution of resistance, with distinct molecular mechanisms of intrinsic resistance including naxD, lpxACD, and stkR gene deletion. On the other hand, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are usually resistant via the PhoP-PhoQ and PmrA-PmrB pathways. Molecular evolutionary analysis of mcr genes was undertaken to show relative relatedness across the ten main lineages. Understanding the molecular determinants of resistance to polymyxins may help develop suitable and effective methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules. Full article

The development of primary liver cancer (PLC) is associated with chronic liver inflammation and the loss of associated tumor suppressor genes, which characterizes inflammation-related tumors. In this study, we aimed to explore the effect of saikosaponin-b2 (SS-b2) on the development of PLC and its effect of the STK4 expression and IRAK1/NF-κB signaling axis. In vitro and in vivo experiments showed that SS-b2 exerted potent anti-inflammatory and antitumor effects. A PLC model was induced in vivo by treating male BALB/c mice with diethylnitrosamine, while an inflammatory model was induced in vitro by exposing RAW 264.7 macrophages to lipopolysaccharides (LPS). After treating cancer mice with SS-b2, the serum levels of alpha-fetoprotein, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly reduced. Ki67 expression also decreased. The carcinomatous lesions of the liver were attenuated. Similar results were observed in liver tissue and RAW 264.7 macrophages, where SS-b2 significantly elevated serine/threonine protein kinase 4 (STK4) expression and decreased the expression of interleukin-1 receptor–associated kinase 1 (IRAK1), nuclear factor-kappaB (NF-κB), and downstream inflammatory cytokines, thus exerting anti-cancer and anti-inflammatory effects. Moreover, we employed siRNA to silence the STK4 expression in HepG2 to investigate the anti-tumor effect of SS-b2 in vitro. The STK4 knockdown would upregulate IRAK1 and thus the activation of NF-κB activity revealed by the increase in the levels of proinflammatory cytokines, consequently impairing SS-b2-induced inhibition of liver cancer development. Consequently, SS-b2 effectively inhibited PLC by upregulating STK4 to suppress the IRAK1/NF-κB signaling axis and is a promising agent for treating this disease. Full article

Cancer metastasis accounts for approximately 90% of cancer deaths, and elucidating markers in metastasis is the first step in its prevention. To characterize metastasis marker genes (MGs) of breast cancer, XGBoost models that classify metastasis status were trained with gene expression profiles from TCGA. Then, a metastasis score (MS) was assigned to each gene by calculating the inner product between the feature importance and the AUC performance of the models. As a result, 54, 202, and 357 genes with the highest MS were characterized as MGs by empirical p-value cutoffs of 0.001, 0.005, and 0.01, respectively. The three sets of MGs were compared with those from existing metastasis marker databases, which provided significant results in most comparisons (p-value < 0.05). They were also significantly enriched in biological processes associated with breast cancer metastasis. The three MGs, SPPL2C, KRT23, and RGS7, showed highly significant results (p-value < 0.01) in the survival analysis. The MGs that could not be identified by statistical analysis (e.g., GOLM1, ELAVL1, UBP1, and AZGP1), as well as the MGs with the highest MS (e.g., ZNF676, FAM163B, LDOC2, IRF1, and STK40), were verified via the literature. Additionally, we checked how close the MGs were to each other in the protein–protein interaction networks. We expect that the characterized markers will help understand and prevent breast cancer metastasis. Full article

The erythropoietin receptor (EPOR) is a transmembrane type I receptor with an essential role in the proliferation and differentiation of erythroid progenitors. Besides its function during erythropoiesis, EPOR is expressed and has protective effect in various non-hematopoietic tissues, including tumors. Currently, the advantageous aspect of EPOR related to different cellular events is still under scientific investigation. Besides its well-known effect on cell proliferation, apoptosis and differentiation, our integrative functional study revealed its possible associations with metabolic processes, transport of small molecules, signal transduction and tumorigenesis. Comparative transcriptome analysis (RNA-seq) identified 233 differentially expressed genes (DEGs) in EPOR overexpressed RAMA 37-28 cells compared to parental RAMA 37 cells, whereas 145 genes were downregulated and 88 upregulated. Of these, for example, GPC4, RAP2C, STK26, ZFP955A, KIT, GAS6, PTPRF and CXCR4 were downregulated and CDH13, NR0B1, OCM2, GPM6B, TM7SF3, PARVB, VEGFD and STAT5A were upregulated. Surprisingly, two ephrin receptors, EPHA4 and EPHB3, and EFNB1 ligand were found to be upregulated as well. Our study is the first demonstrating robust differentially expressed genes evoked by simple EPOR overexpression without the addition of erythropoietin ligand in a manner which remains to be elucidated. Full article

Lung cancer remains the leading cancer-related death across North America. Imaging is fundamental. Recently, healthcare disparities came into research focus. Our aim was to explore disparity from an imaging, genetic, and outcome perspective. We utilized the AACR Project GENIE Biopharma Consortium (BPC) dataset v 1.1 to build a collated NSCLC dataset. Descriptive and analytical statistics were applied according to data characteristics. From 1849 patients, mean age was 64.4 y (±10.5), 58% (n = 1065) were female, 23% (n = 419) never smoked, 84% (n = 1545) were of white race, and 57% (n = 1052) were < stage III. No difference (p > 0.05) was found for baseline imaging by race. White race showed higher 3-month surveillance imaging (p = 0.048) and a baseline stage < IV (OR 0.61). KRAS (33.3 vs. 17.9%), STK11 (14.8 vs. 7.3%), and KEAP1 (13.3 vs. 5.3%) mutations were predominant among white patients while EGFR mutation (19.2 vs. 44.1%) was less predominant. Mutations in TP53 or KEAP1 had worse PFS and OS. The latter was also reduced in STK11, KRAS + STK11, and KRAS + KEAP1 mutations. Meanwhile, EGFR mutation had increased OS. Multivariate analysis showed that progression on imaging at 3 or 6 months (HR 1.69 and 1.43, respectively), TP53 (HR 1.37) and KRAS (HR 1.26) had lower OS while EGFR and LRP1B (HR 0.69 and 0.39, respectively) had higher OS. No racial disparity at baseline imaging was observed. Higher initial stages among non-white patients might reflect inequalities in accessing healthcare. However, race wasn’t associated to OS. Finally, progression in imaging at 3 or 6 months showed the higher hazard ratios for death. Full article

Brassinosteroids (BRs) are important for plant growth and development, with BRI1 and BAK1 kinases playing an important role in BR signal transduction. Latex from rubber trees is crucial for industry, medicine and defense use. Therefore, it is beneficial to characterize and analyze HbBRI1 and HbBAK1 genes to improve the quality of the resources obtained from Hevea brasiliensis (rubber tree). Based on bioinformatics predictions and rubber tree database, five HbBRI1s with four HbBAK1s were identified and named HbBRI1~HbBRL3 and HbBAK1a~HbBAK1d, respectively, which were clustered in two groups. HbBRI1 genes, except for HbBRL3, exclusively contain introns, which is convenient for responding to external factors, whereas HbBAK1b/c/d contain 10 introns and 11 exons, and HbBAK1a contains eight introns. Multiple sequence analysis showed that HbBRI1s include typical domains of the BRI1 kinase, indicating that HbBRI1s belong to BRI1. HbBAK1s that possess LRR and STK_BAK1_like domains illustrate that HbBAK1s belong to the BAK1 kinase. BRI1 and BAK1 play an important role in regulating plant hormone signal transduction. Analysis of the cis-element of all HbBRI1 and HbBAK1 genes identified hormone response, light regulation and abiotic stress elements in the promoters of HbBRI1s and HbBAK1s. The results of tissue expression patterns indicate that HbBRL1/2/3/4 and HbBAK1a/b/c are highly expressed in the flower, especially HbBRL2-1. The expression of HbBRL3 is extremely high in the stem, and the expression of HbBAK1d is extremely high in the root. Expression profiles with different hormones show that HbBRI1 and HbBAK1 genes are extremely induced by different hormone stimulates. These results provide theoretical foundations for further research on the functions of BR receptors, especially in response to hormone signals in the rubber tree. Full article

Soybean (Glycine max (Linn.) Merr.) is a widely-cultivated crop, the yield of which is markedly affected by adverse environmental conditions. Soil salinization, in particular, has led to the degradation of agricultural land, resulting in poor plant growth and decreased crop yields. In plants, serine/threonine protein kinases (STKs) are involved in the plant response to a variety of abiotic stresses. Our previous study identified a transcription factor (GmWRKY20) involved in plant stress resistance, which can directly regulate the expression of GmSTK12. Here, we investigated the effect of the stress-responsive gene GmSTK12 (Glyma.12g198200), which encodes a serine/threonine protein kinase, on soybean salt tolerance. Overall, the overexpression of GmSTK12 (GmSTK12-OE) resulted in increased salt tolerance. Under salt stress, GmSTK12-OE soybeans exhibited significantly increased chlorophyll and proline (PRO) contents; decreased relative electrical conductivity; decreased malondialdehyde (MDA) and superoxide anion (O2⁻) contents; and increased activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). The nitroblue tetrazolium chloride (NBT) staining experiment further confirmed the reduced accumulation of reactive oxygen species (ROS) in GmSTK12-OE soybean leaves. We further determined the Na⁺ and K⁺ contents in soybean leaves and roots and found that the Na⁺ content and Na⁺/K⁺ ratio in GmSTK12-OE soybean leaves and roots were significantly lower than those of WT (williams82) soybeans. Furthermore, quantitative real-time PCR (qRT-PCR) analysis revealed that the expression of three SOS pathway genes (GmSOS1, GmSOS2a, and GmSOS2b) was upregulated in GmSTK12-OE soybeans under salt stress. Taken together, the results indicate that GmSTK12 is involved in the mechanism of soybean response to salt stress. Full article

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and cognitive functions. It is still unknown how gene expression changes in single-cell in different spatial locations of the hippocampus of Parkinson’s disease. The purpose of this study was to analyze the gene expression features of single cells in different spatial locations of mouse hippocampus, and to explore the effects of gene expression regulation on learning and memory mechanisms. Here, we obtained 74 single-cell samples from different spatial locations in a mouse hippocampus through microdissection technology, and used single-cell RNA-sequencing and spatial transcriptome sequencing to visualize and quantify the single-cell transcriptome features of tissue sections. The results of differential expression analysis showed that the expression of Sv2b, Neurod6, Grp and Stk32b genes in a hippocampus single cell at different locations was significantly different, and the marker genes of CA1, CA3 and DG subregions were identified. The results of gene function enrichment analysis showed that the up-regulated differentially expressed genes Tubb2a, Eno1, Atp2b1, Plk2, Map4, Pex5l, Fibcd1 and Pdzd2 were mainly involved in neuron to neuron synapse, vesicle-mediated transport in synapse, calcium signaling pathway and neurodegenerative disease pathways, thus affecting learning and memory function. It revealed the transcriptome profile and heterogeneity of spatially located cells in the hippocampus of PD for the first time, and demonstrated that the impaired learning and memory ability of PD was affected by the synergistic effect of CA1 and CA3 subregions neuron genes. These results are crucial for understanding the pathological mechanism of the Parkinson’s disease and making precise treatment plans. Full article