Emergence of a novel pathogenic porcine G1P[7] rotavirus in China.

Among group A rotaviruses (RVAs), the G1 genotype is the main genotype causing diarrhea in children, but it has rarely been reported in pigs. During our epidemiological investigation, we detected G1P[7] rotavirus infection in piglets across several provinces in China and then isolated a porcine G1P[7] rotavirus strain (CN1P7). Sequencing revealed that the virus constellation was G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analyses revealed that CN1P7 most likely emerged due to genetic reassortment among porcine, human, giant panda and dog rotavirus strains. In vivo experiments were conducted on two-day-old piglets, which revealed that the CN1P7 strain was pathogenic to piglets. The virus was shed through the digestive tract and respiratory tract. In addition to the intestine, the CN1P7 strain displayed extraintestinal tropisms in piglets. Histopathological analysis revealed that the lung and small intestine were the targets of CN1P7. This study is the first to explore the molecular and pathogenic characterization of a pig-origin G1P[7] rotavirus.

Elevation of IL-8 secretion induced by PEDV infection via NF-κB signaling pathway.

Porcine epidemic diarrhea virus (PEDV) is associated with severe enteritis, which contributes to high mortality in piglets. The aim of this study was to describe molecular mechanisms associated with proinflammatory cytokine(s) production during PEDV infection. We showed that infection of porcine intestine epithelial cell clone J2 (IPEC-J2) with PEDV induces a gradual increase in interleukin 8 (IL-8) production at different time points, as well as infection of Vero E6 with PEDV. The secretion of IL-8 in these two cell lines infected with PEDV is related to the activation of NF-κB. Furthermore, the cells expressing PEDV M or E protein can induce the upregulation of IL-8. These findings suggest that the IL-8 production can be the initiator of inflammatory response by the host cells upon PEDV infection.

Mycenabrunnescens (Basidiomycota, Mycenaceae), a new species of Mycena sect. Pterigenae from China.

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

Macrophage-based cancer immunotherapy: challenges and opportunities.

Macrophages play crucial roles in the tumor microenvironment (TME), exerting diverse functions ranging from promoting tumor growth and metastasis to orchestrating anti-tumor immune responses. Their plasticity allows them to adopt distinct activation states, often called M1-like (pro-inflammatory) and M2-like (anti-inflammatory or pro-tumoral), significantly influencing tumor progression and response to therapy. Harnessing the potential of macrophages in cancer immunotherapy has emerged as a promising strategy, with increasing interest in targeting these cells directly or modulating their functions within the TME. This review explores the intricate interplay between macrophages, the TME, and immunotherapeutic approaches. We discuss the dynamic phenotypic and functional heterogeneity of tumor-associated macrophages (TAMs), their impact on disease progression, and the mechanisms underlying their response to immunotherapy. Furthermore, we highlight recent advancements in macrophage-based immunotherapeutic strategies, including macrophage-targeting agents, adoptive cell transfer, and engineering approaches. Understanding the complex crosstalk between macrophages and the TME is essential for developing effective immunotherapeutic interventions that exploit the immunomodulatory functions of macrophages to enhance anti-tumor immunity and improve clinical outcomes for cancer patients.

One Stone, Three Birds: Feasible Tuning of Barrier Heights Induced by Hybridized Interface in Free-Standing PEDOT@Bi2Te3 Thermoelectric Films.

Converting low-grade thermal energy into electrical energy is crucial for the development of modern smart wearable energy technologies. The free-standing films of PEDOT@Bi2Te3 prepared by tape-casting hold promise for flexible thermoelectric technology in self-powered sensing applications. Bi2Te3 nanosheets fabricated by the solvothermal method are tightly connected with flat-arranged PEODT molecules, forming an S-Bi bonded interface in the composite materials, and the bandgap is reduced to 1.63 eV. Compared with the PEDOT film, the mobility and carrier concentration of the composite are significantly increased at room temperature, and the conductivity reaches 684 S/cm. Meanwhile, the carrier concentration decreased sharply at 360 K indicating the creation of defect energy levels during the interfacial reaction of the composites, which increased the Seebeck coefficient. The power factor was improved by 68.9% compared to PEDOT. In addition, the introduction of Bi2Te3 nanosheets generated defects and multidimensional interfaces in the composite film, which resulted in weak phonon scattering in the conducting polymer with interfacial scattering. The thermal conductivity of the film is decreased and the ZT value reaches 0.1. The composite film undergoes 1500 bending cycles with a 14% decrease in conductivity and has good flexibility. This self-supporting flexible thermoelectric composite film has provided a research basis for low-grade thermal energy applications.

The circular RNA circSLC16A10 alleviates diabetic retinopathy by improving mitochondrial function via the miR-761-5p/MFN2 axis.

It has been demonstrated that circular RNAs (circRNAs) are associated with the development of diabetic retinopathy (DR). Nevertheless, the function of circSLC16A10 in the development of DR remains unclear. In order to investigate the role of circSLC16A10, we employed cell and animal models of DR. An analysis of a public database revealed that hsa_circSLC16A10 was expressed at lower levels in DR patients than in diabetic patients without DR or healthy controls. Additionally, the level of hsa_circSLC16A10 was lower in high glucose (HG)-exposed ARPE-19 cells and diabetic mice. hsa_circSLC16A10 was observed to be mainly distributed in the cytoplasm. Moreover, overexpression of hsa_circSLC16A10 alleviated HG-induced endoplasmic reticulum stress and cell apoptosis in vitro. Furthermore, overexpression of hsa_circSLC16A10 ameliorated HG-induced mitochondrial dysfunction, as evidenced by improvements in mitochondrial structure and function. hsa_circSLC16A10 acted as a hsa-miR-761-5p sponge to increase MFN2 expression. MFN2 knockdown or hsa-miR-761-5p overexpression partially reversed the protective effect of hsa_circSLC16A10 in vitro. The protective effect of mmu_circSLC16A10 against DR was confirmed in an animal model of DR. These findings indicate that circSLC16A10 may regulate DR progression by improving mitochondrial function via the miR-761-5p/MFN2 axis.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Discrimination of relatedness drives rice flowering and reproduction in cultivar mixtures.

The improvement of performance and yield in both cultivar and species mixtures has been well established. Despite the clear benefits of crop mixtures to agriculture, identifying the critical mechanisms behind performance increases are largely lacking. We experimentally demonstrated that the benefits of rice cultivar mixtures were linked to relatedness-mediated intraspecific neighbour recognition and discrimination under both field and controlled conditions. We then tested biochemical mechanisms of responses in incubation experiments involving the addition of root exudates and a root-secreted signal, (-)-loliolide, followed by transcriptome analysis. We found that closely related cultivar mixtures increased grain yields by modifying root behaviour and accelerating flowering over distantly related mixtures. Importantly, these responses were accompanied by altered concentration of signalling (-)-loliolide that affected rice transcriptome profiling, directly regulating root growth and flowering gene expression. These findings suggest that beneficial crop combinations may be generated a-priori by manipulating neighbour genetic relatedness in rice cultivar mixtures and that root-secreted (-)-loliolide functions as a key mediator of genetic relatedness interactions. The ability of relatedness discrimination to regulate rice flowering and yield raises an intriguing possibility to increase crop production.

Frailty and all-cause and cancer-related mortality in cancer patients: A prospective cohort study.

PURPOSE: To evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. METHODS: We gathered baseline data from NHANES (1999-2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. RESULTS: Ultimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956-1.800, P = 0.092; HRs = 1.462, 0.811-2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617-3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370-4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073-4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475-2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. CONCLUSIONS: Pre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.

Piperine inhibits the proliferation of colorectal adenocarcinoma by regulating ARL3-mediated endoplasmic reticulum stress.

Colorectal adenocarcinoma (COAD) is a significant cause of cancer-related mortality worldwide, necessitating the identification of novel therapeutic targets and treatments. This research aimed to investigate the role of ARL3 in COAD progression and to explore the effects of Piperine on ARL3 expression, cell proliferation, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress. Bioinformatics analysis of The Cancer Genome Atlas (TCGA)-COAD, GSE39582, and GSE44861 datasets assessed ARL3 expression levels. Immunohistochemical data from the Human Protein Atlas (HPA) database confirmed ARL3 overexpression in COAD. The association of ARL3 with COAD clinical parameters and prognosis was also examined. COAD cells were treated with Piperine, and in vitro assays evaluated cell proliferation, apoptosis, EMT marker expression, and ER stress responses. ARL3 overexpression in COAD correlated with poor prognosis and varied across pathological stages. Piperine treatment inhibited COAD cell proliferation in a concentration- and time-dependent manner, as indicated by reduced Ki-67 levels and decreased colony-forming ability. Piperine induced S-phase cell cycle arrest and facilitated apoptosis in COAD cells, evidenced by changes in Bax, Bcl-2, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) levels. Moreover, Piperine downregulated ARL3 expression in COAD cells, thereby suppressing transforming growth factor beta (TGF-ß)-induced EMT. Additionally, Piperine attenuated the ARL3-mediated ER stress response, significantly reducing binding immunoglobulin protein (BiP), inositol-requiring enzyme 1 alpha (p-IRE1α), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) levels. Piperine exerted anti-cancer effects in COAD by modulating ARL3 expression, disrupting cell cycle progression, inhibiting the EMT pathway, and regulating ER stress. These findings suggest that Piperine holds promise as a therapeutic agent for COAD through its targeting of ARL3.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.

Rapid diagnosis of alveolar echinococcosis from lung puncture sample using metagenomic next-generation sequencing: a case report.

INTRODUCTION: Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. CASE PRESENTATION: A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. CONCLUSION: This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.

Identification and validation of Cystatin A as a novel promising therapeutic target for gastric cancer.

Background: The effect of pharmacological treatment of gastric cancer (GC) is limited, thus, it holds significant scientific importance to thoroughly investigate the molecular mechanisms underlying GC development and identify novel molecules capable of substantially extending patients' survival. This study utilized bioinformatics techniques to identify 11 genes associated with recurrence-free survival (RFS) in GC patients and investigated the potential biological functions of these genes through single-cell transcriptomic analysis. Subsequently, a single gene Cystatin A (CSTA) was selected for further analysis to explore its impact on signaling pathways and treatment. Methods: Differentially expressed genes (DEGs) were identified and overlapped in the analysis of RFS to identify potential prognostic genes for GC patients, based on data from the Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) and GSE54129. Subsequently, a prognostic model based on RFS in GC patients was established. Single-cell sequencing data were employed to explore the potential functions of these model genes. CSTA, one of the RFS-related genes, was further investigated using immunohistochemistry (IHC), Cell Counting Kit 8 (CCK-8), transwell, scratch, colony formation assays, flow cytometry, and Western blotting methods. Results: Through bioinformatics analysis, we identified 23 RFS-related genes in GC. Using the least absolute shrinkage and selection operator (LASSO)-Cox method, an RFS prognostic model was developed which pinpointed 11 GC prognosis-related (GPR) genes as significant factors influencing RFS in GC patients. The single-cell analysis revealed their potential role in affecting differentiation and maturation of pre-fibroblasts thereby impacting RFS in GC patients. CSTA exhibited low expression levels in GC tissues. Overexpression of CSTA promoted apoptosis in GC cells through the caspase-dependent apoptotic pathway and enhanced their response to cisplatin via this same pathway. Conclusions: The 11 GPR genes are primarily enriched within a specific type of stromal cell exhibiting heightened communication, metabolism, and differentiation levels. The gene signature of these stromal cells has implications for patient prognosis. Additionally, CSTA, a gene related to prognosis, has been shown to influence apoptosis levels in GC cells.

The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.

Ferroptosis is an iron-dependent programmed cell death process that involves lipid oxidation via the Fenton reaction to produce lipid peroxides, causing disruption of the lipid bilayer, which is essential for cellular survival. Ferroptosis has been implicated in the occurrence and treatment response of various types of cancer, and targeting ferroptosis has emerged as a promising strategy for cancer therapy. However, cancer cells can escape cellular ferroptosis by activating or remodeling various signaling pathways, including oxidative stress pathways, thereby limiting the efficacy of ferroptosis-activating targeted therapy. The key anti-oxidative transcription factor, nuclear factor E2 related factor 2 (Nrf2 or NFE2L2), plays a dominant role in defense machinery by reprogramming the iron, intermediate, and glutathione peroxidase 4 (GPX4)-related network and the antioxidant system to attenuate ferroptosis. In this review, we summarize the recent advances in the regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy and explore the prospect of combining Nrf2 inhibitors and ferroptosis inducers as a promising cancer treatment strategy.

Idiopathic ventricular arrhythmia originating from the vicinity of lateral tricuspid annulus: the precise origin and anatomical concerns.

BACKGROUND: Although the electrcardiographic and electrophysiological properties of ventricular arrhythmias (VA) from the vicinity of lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed. OBJECTIVE: To describe the precise origin of lateral TA-VA and the relevant anatomy. METHODS: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomical reconstruction, mapping, and ablation. RESULTS: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along lateral TA. The muscular bundle was documented in all patients (100%) within the sub-valvular enfoldment with an average number and diameter of 4±2 and 4.10±0.73mm, respectively. Initial ablation was attempted via the antegrade approach in 15 patients but succeeded in none. To reach the ventricular side of TA, the catheter needed to enter ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 (80.9%) patients with a local activation time of -26.78±4.63ms. The VAs were eliminated after an average of 4±2 seconds of ablations. CONCLUSION: The ventricular adjacent to the lateral TA exhibits a sub-valvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Analysis of pulmonary microecology and clinical characteristics of patients carrying human herpesvirus.

Aim: To investigate the impact of human herpes virus (HHV) carriage on lung microbiota, and its correlation with clinical features and laboratory indicators in patients. Methods: Retrospective analysis was conducted on 30 outpatient lung infection cases, which were divided into HHV (n = 15) and non-HHV (n = 15) groups. mNGS detected microbial composition. Microbial diversity and abundance were tested using Shannon and Chao1 indices. Their relationship with laboratory indicators were explored. Results: Significant differences in microbial abundance and distribution were found between two groups (p < 0.05). Moreover, HHV group showed negative correlations (p < 0.05) between Prevotella, Porphyromonas, Streptococcus and basophil/eosinophil percentages. Conclusion: HHV carriage impacts lung microbiota, emphasizing the need for clinicians to pay attention to HHV reactivation in outpatient lung infection patients.

This study looked at how a common virus called human herpesvirus (HHV) affects the bacteria in our lungs. We wanted to see if HHV is linked to how sick we feel and what tests show. We split 30 people who had lung infections into two groups ­ 15 with HHV and 15 without ­ and checked how sick they felt, did some tests, and looked at the types of bacteria in their lungs. Both groups felt similarly sick and got better with medicine, but people with HHV had fewer of a certain type of blood cell. People with and without HHV also had different types of bacteria in their lungs. This study helps us understand why people get sick with lung infections and how to make them better. It might also help doctors decide how to treat people with lung infections.

Exploring prognostic values of DNA ploidy, stroma-tumor fraction and nucleotyping in stage II colon cancer patients.

PURPOSE: To assess the prognostic value of three novel biomarkers, DNA ploidy, stroma-tumor fraction, and nucleotyping, seeking for more accurate stratification in stage II colon cancer. METHODS: A total of 417 patients with complete follow up information were enrolled in this study and divided into three clinical risk groups. IHC was performed to examine MSI status. DNA ploidy, stroma and nucleotyping were estimated using automated digital imaging system. Kaplan-Meier survival curves, Cox proportional hazards regression models, and correlation analyses were carried out to process our data. RESULTS: In the whole cohort of stage II colon cancer, nucleotyping and DNA ploidy were significant prognostic factors on OS in univariate analyses. The combination of nucleotyping and DNA ploidy signified superior OS and DFS. Difference was not significant between low-stroma and high-stroma patients. In multivariable analyses, nucleotyping and the combination of nucleotyping and DNA ploidy were proven the dominant contributory factors for OS. In the low-risk group, we found the combination of nucleotyping and DNA ploidy as the independent prognostic factor statistically significant in both univariate and multivariable, while in the high-risk group, the nucleotyping. CONCLUSIONS: Our study has proven nucleotyping and the combination of DNA ploidy and nucleotyping as independent prognostic indicators, thus expanding the application of nucleotyping as a predictor from high risk stage II colon cancer to whole risks.

Chemical Dynamics of Selenium Nanoparticles in Archaeal Systems.

Methanogenic archaea, characterized by their cell membrane lipid molecules consisting of isoprenoid chains linked to glycerol-1-phosphate via ether bonds, exhibit exceptional adaptability to extreme environments. However, this distinct lipid architecture also complicates the interactions between methanogenic archaea and nanoparticles. This study addresses this challenge by exploring the interaction and transformation of selenium nanoparticles (SeNPs) within archaeal Methanosarcina acetivorans C2A. We demonstrated that the effects of SeNPs are highly concentration-dependent, with chemical stimulation of cellular processes at lower SeNPs concentrations as well as oxidative stress and metabolic disruption at higher concentrations. Notably, we observed the formation of a protein corona on SeNPs, characterized by the selective adsorption of enzymes critical for methylotrophic methanogenesis and those involved in selenium methylation, suggesting potential alterations in protein function and metabolic pathways. Furthermore, the intracellular transformation of SeNPs into both inorganic and organic selenium species highlighted their bioavailability and dynamic transformation within archaea. These findings provide vital insights into the nano-bio interface in archaeal systems, contributing to our understanding of archaeal catalysis and its broader applications.