Metabolomic analysis of rumen-protected branched-chain amino acids in primiparous dairy cows.

Introduction: Peripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows. Methods: In this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal. Results: In comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines. Discussion: In summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Impact of deoxynivalenol on rumen function, production, and health of dairy cows: Insights from metabolomics and microbiota analysis.

Deoxynivalenol contamination in feed and food, pervasive from growth, storage, and processing, poses a significant risk to dairy cows, particularly when exposed to a high-starch diet; however, whether a high-starch diet exacerbates these negative effects remains unclear. Therefore, we investigated the combined impact of deoxynivalenol and dietary starch on the production performance, rumen function, and health of dairy cows using metabolomics and 16 S rRNA sequencing. Our findings suggested that both high- and low-starch diets contaminated with deoxynivalenol significantly reduced the concentration of propionate, isobutyrate, valerate, total volatile fatty acids (TVFA), and microbial crude protein (MCP) concentrations, accompanied by a noteworthy increase in NH3-N concentration in vitro and in vivo (P < 0.05). Deoxynivalenol altered the abundance of microbial communities in vivo, notably affecting Oscillospiraceae, Lachnospiraceae, Desulfovibrionaceae, and Selenomonadaceae. Additionally, it significantly downregulated lecithin, arachidonic acid, valine, leucine, isoleucine, arginine, and proline metabolism (P < 0.05). Furthermore, deoxynivalenol triggered oxidative stress, inflammation, and dysregulation in immune system linkage, ultimately compromising the overall health of dairy cows. Collectively, both high- and low-starch diets contaminated with deoxynivalenol could have detrimental effects on rumen function, posing a potential threat to production performance and the overall health of cows. Notably, the negative effects of deoxynivalenol are more pronounced with a high-starch diet than a low-starch diet.

Toward Ultrastable Metal Anode/Li6PS5Cl Interface via an Interlayer as Li Reservoir.

All-solid-state sulfide-based Li metal batteries are promising candidates for energy storage systems. However, thorny issues associated with undesired reactions and contact failure at the anode interface hinder their commercialization. Herein, an indium foil was endowed with a formed interlayer whose surface film is enriched with LiF and LiIn phases via a feasible prelithiation route. The lithiated alloy of the interlayer can regulate Li+ flux and charge distribution as a Li reservoir, benefiting uniform Li deposition. Meanwhile, it can suppress the reductive decomposition of the Li6PS5Cl electrolyte and maintain sufficient solid-solid contact. In situ impedance spectra reveal that constant interface impedance and fast charge transfer are realized by the interlayer. Further, long-term Li stripping/plating over 2000 h at 2.55 mA cm-2 is demonstrated by this anode. All-solid-state cells employing a LiCoO2 cathode and the Pre In anode can work for over 700 cycles with a capacity retention of 96.15% at 0.5 C.

Molecular characteristics of multiple primary pulmonary nodules under a three-dimensional reconstruction model and relevant multi-omics analyses: a case report.

Background: In addition to CT images and pathological features, many other molecular characteristics remain unknown about multiple primary lung cancer (MPLC) from intrapulmonary metastatic lung cancer. Case presentation: In this study, we reported a patient with an early-stage MPLC with both adenocarcinoma in situ (AIS) subtype and minimally invasive adenocarcinoma (MIA) subtype. The patient was diagnosed with more than 10 nodules and underwent precise surgery assisted by three-dimensional (3D) reconstruction at the left upper lung lobe. Whole-exome sequencing (WES) and multiple immunohistochemistry (mIHC) were performed to reveal the genomic profiling and tumor microenvironments of multiple nodules in this patient with MPLC. Based on 3D reconstruction location information, we found that the genomic and pathological results of adjacent lymph nodes were quite different. On the other hand, PD-L1 expression and the proportion of infiltrating lymphocytes in tumor microenvironments were all at a low status and did not vary in adjacent lymph nodes. Additionally, maximum diameter and tumor mutational burden levels were found to be significantly associated with CD8+ T cell proportion (p<0.05). Besides, CD163+ macrophages and CD4+ T cell proportion were higher in MIA nodules than in AIS nodules (p<0.05). This patient reached a recurrence-free survival of 39 months. Conclusion: Generally, in addition to CT imaging and pathological results, genomic profiling and tumor microenvironments may facilitate identifying the potential molecular mechanisms and clinical outcomes in patients with early-stage MPLC.

Electrochemical Performances of Nickel-Rich Single-Crystal LiNi0.83 Co0.12 Mn0.05 O2 Cathode Material for Lithium-Ion Batteries Synthesized by Tuning Li+ /Ni2+ Mixing.

Single-crystal nickel-rich materials are promising alternatives to polycrystalline cathodes owing to their excellent structure stability and cycle performance while the cathode material usually appears high cation mixing, which may have a negative effect on its electrochemical performance. The study presents the structural evolution of single-crystal LiNi0.83 Co0.12 Mn0.05 O2 in the temperature-composition space using temperature-resolved in situ XRD and the cation mixing is tuned to improve electrochemical performances. The as-synthesized single-crystal sample shows high initial discharge specific capacity (195.5 mAh g-1 at 1 C), and excellent capacity retention (80.1 % after 400 cycles at 1 C), taking account of lower structure disorder (Ni2+ occupying Li sites is 1.56 %) and integrated grains with an average of 2-3 µm. In addition, the single-crystal material also displays a superior rate capability of 159.1 mAh g-1 at the rate of 5 C. This excellent performance is attributed to the rapid Li+ transportation within the crystal structure with fewer Ni2+ cations in Li layer as well as intactly single grains. In sum, the regulation of Li+ /Ni2+ mixing provides a feasible strategy for boosting single-crystal nickel-rich cathode material.

RRS1 shapes robust root system to enhance drought resistance in rice.

A strong root system facilitates the absorption of water and nutrients from the soil, to improve the growth of crops. However, to date, there are still very few root development regulatory genes that can be used in crop breeding for agriculture. In this study, we cloned a negative regulator gene of root development, Robust Root System 1 (RRS1), which encodes an R2R3-type MYB family transcription factor. RRS1 knockout plants showed enhanced root growth, including longer root length, longer lateral root length, and larger lateral root density. RRS1 represses root development by directly activating the expression of OsIAA3 which is involved in the auxin signaling pathway. A natural variation in the coding region of RRS1 changes the transcriptional activity of its protein. RRS1T allele, originating from wild rice, possibly increases root length by means of weakening regulation of OsIAA3. Knockout of RRS1 enhances drought resistance by promoting water absorption and improving water use efficiency. This study provides a new gene resource for improving root systems and cultivating drought-resistant rice varieties with important values in agricultural applications.

Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer.

Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.

The mechanism of lncRNAs in the crosstalk between epithelial-mesenchymal transition and tumor microenvironment for early colon adenocarcinoma based on molecular subtyping.

A large number of colon adenocarcinoma (COAD) patients are already advanced when diagnosed. In this study, we aimed to further understand the mechanism of tumor development in early COAD by focusing on epithelial-mesenchymal transition (EMT) and long non-coding RNAs (lncRNAs). Expression profiles of early COAD patients were obtained from public databases. EMT-related lncRNAs were used as a basis for constructing molecular subtypes through unsupervised consensus clustering. Genomic features, pathways and tumor microenvironment (TME) were compared between two subtypes. LncATLAS database was applied to analyze the relation between lncRNAs and transcription factors (TFs). First order partial correlation analysis was conducted to identify key EMT-related lncRNAs.C1 and C2 subtypes with distinct prognosis were constructed. Oncogenic pathways such as EMT, KRAS signaling, JAK-STAT signaling, and TGF-ß signaling were significantly enriched in C2 subtype. Higher immune infiltration and expression of immune checkpoints were also observed in C2 subtype, suggesting the key EMT-related lncRNAs may play a critical role in the modulation of TME. In addition, JAK-STAT signaling pathway was obviously enriched in upregulated TFs in C2 subtype, which indicated a link between key lncRNAs and JAK-STAT signaling that may regulate TME. The study further expanded the research on the role of EMT-related lncRNAs in the early COAD. The six identified EMT-related lncRNAs could serve as biomarkers for early screening COAD.

Chemically Induced Activity Recovery of Isolated Lithium in Anode-free Lithium Metal Batteries.

The anode-free lithium metal battery is considered to be an excellent candidate for the new generation energy storage system because of its higher energy density and safety than the traditional lithium metal battery. However, the continuous generation of SEI or isolated Li hinders its practical application. In general, the isolated Li is considered electrochemically inactive because it loses electrical connection with the current collector. Here we show an abnormal phenomenon that the lost capacity appears to be recovered after cycles when the isolated Li reconnects with a deposited Li metal layer. The isolated Li reconnection is ascribed to the chemical induction of the block copolymer coating. The migration of Li+ is affected by the electron delocalization and the electron cloud density of the polymer, which determine the conversion direction of Li+. Based on the mechanism, we propose a strategy to slow down the capacity decay of the anode-free lithium metal battery.

Genomic and Immunological Characterization of Pyroptosis in Lung Adenocarcinoma.

Pyroptosis is a programmed cell death that may either promote or hinder cancer growth under different circumstances. Pyroptosis-related genes (PRGs) could be a useful target for cancer therapy, and are uncommon in lung adenocarcinoma (LUAD). The expression profiles, mutation data and clinical information of LUAD patients were included in this study. A pyroptosis-related prognostic risk score (PPRS) model was constructed by performing Cox regression, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) analysis to score LUAD patients. Somatic mutation and copy number variation (CNV), tumor immunity, and sensitivity to immunotherapy/chemotherapy were compared between different PPRS groups. Clinical parameters of LUAD were combined with PPRS to construct a decision tree and nomogram. Red module was highly positively correlated with pyroptosis. Seven genes (FCRLB, COTL1, GNG10, CASP4, DOK1, CCR2, and AQP8) were screened from the red module to construct a PPRS model. Significantly lower overall survival (OS), higher incidence of somatic mutation and CNV, elevated infiltration level of the immune cell together with increased probability of immune escape were observed in LUAD patients with higher PPRS, and were more sensitive to Cisplatin, Docetaxel, and Vinorelbine. We constructed a new PPRS model for patients with LUAD. The model might have clinical significance in the prediction of the prognosis of patients with LUAD and in the efficacy of chemotherapy and immunotherapy.

Comprehensive Analysis of Histone Modifications in Hepatocellular Carcinoma Reveals Different Subtypes and Key Prognostic Models.

Histone modification, an important epigenetic mechanism, is related to the carcinogenesis of hepatocellular carcinoma (HCC). In three datasets, we screened 88 epigenetic-dysregulated PCGs (epi-PCGs) , which were significantly associated with HCC survival and could cluster HCC into three molecular subtypes. These subtypes were associated with prognosis, immunomodulatory alterations, and response to different treatment strategies. Based on 88 epi-PCGs in the TCGA training set, a risk prediction model composed of 4 epi-PCGs was established. The model was closely related to the clinicopathological features and showed a strong predictive ability in different clinical subgroups. In addition, the risk prediction model was an independent prognostic factor for patients with HCC. The significance of epi-PCGs in HCC is revealed by our data analysis.

Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer.

To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis coli (APC) gene mutations in CRC patients. A total of 238 Chinese CRC patients was retrospectively identified and analyzed for clinical features and gene alternations in APC-mutant type (MT) and APC-wild-type (WT) groups. Clinical responses were then evaluated from the public TCGA database and MSKCC immunotherapy database. Although programmed cell death ligand 1 (PD-L1) level, MSI status, loss of heterogeneity at the human leukocyte antigen (HLA LOH), and tumor neoantigen burden (TNB) level were not statistically different between the APC-MT group and APC-WT group, tumor mutation burden (TMB) level was significantly higher in APC-MT patients (P < 0.05). Furthermore, comutation analysis for APC mutations revealed co-occurring genomic alterations of PCDHB7 and exclusive mutations of CTNNB1, BRAF, AFF3, and SNX25 (P < 0.05). Besides, overall survival from MSKCC-CRC cohort was longer in the APC-WT group than in the APC-MT group (HR 2.26 (95% CI 1.05-4.88), P < 0.05). Furthermore, most of patients in the APC-WT group were detected as high-grade immune subtypes (C2-C4) comparing with those in the APC-MT group. In addition, the percentages of NK T cells, Treg cells, and fibroblasts cells were higher in APC-WT patients than in APC-MT patients (P < 0.05). In summary, APC mutations might be associated with poor outcomes for immunotherapy in CRC patients regardless of MSI status. This study suggested APC gene mutations might be a potential predictor for immunotherapy in CRC.

Exploring the Interplay between Metabolism and Tumor Microenvironment Based on Four Major Metabolism Pathways in Colon Adenocarcinoma.

Tumor metabolism plays a critical role in tumor progression. However, the interaction between metabolism and tumor microenvironment (TME) has not been comprehensively revealed in colon adenocarcinoma (COAD). We used unsupervised consensus clustering to establish three molecular subtypes (clusters) based on the enrichment score of four major metabolism pathways in TCGA-COAD dataset. GSE17536 was used as a validation dataset. Single-cell RNA sequencing data (GSE161277) was employed to further verify the reliability of subtyping and characterize the correlation between metabolism and TME. Three clusters were identified and they performed distinct prognosis and molecular features. Clust3 had the worst overall survival and the highest enrichment score of glycolysis. 86 differentially expressed genes (DEGs) were identified, in which 11 DEGs were associated with favorable prognosis and 75 DEGs were associated with poor prognosis. Striking correlations were observed between hypoxia and glycolysis, clust3 and hypoxia, and clust3 and angiogenesis (P < 0.001).We constructed a molecular subtyping system which was effective and reliable for predicting COAD prognosis. The 86 identified key DEGs may be greatly involved in COAD progression, and they provide new perspectives and directions for further understanding the mechanism of metabolism in promoting aggressive phenotype by interacting with TME.

BUB1 Is Identified as a Potential Therapeutic Target for Pancreatic Cancer Treatment.

Pancreatic cancer is one of the most challenging cancer types in clinical treatment worldwide. This study aimed to understand the tumorigenesis mechanism and explore potential therapeutic targets for patients with pancreatic cancer. Single-cell data and expression profiles of pancreatic cancer samples and normal tissues from multiple databases were included. Comprehensive bioinformatics analyses were applied to clarify tumor microenvironment and identify key genes involved in cancer development. Immense difference of cell types was shown between tumor and normal samples. Four cell types (B cell_1, B cell_2, cancer cell_3, and CD1C+_B dendritic cell_3) were screened to be significantly associated with prognosis. Three ligand-receptor pairs, including CD74-MIF, CD74-COPA, and CD74-APP, greatly contributed to tumorigenesis. High expression of BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase) was closely correlated with worse prognosis. CD1C+_B dendritic cell_3 played a key role in tumorigenesis and cancer progression possibly through CD74-MIF. BUB1 can serve as a prognostic biomarker and a therapeutic target for patients with pancreatic cancer. The study provided a novel insight into studying the molecular mechanism of pancreatic cancer development and proposed a potential strategy for exploiting new drugs.

Genomic correlates of programmed cell death ligand 1 (PD-L1) expression in Chinese lung adenocarcinoma patients.

BACKGROUND: Although PD-L1 expression is a crucial predictive biomarker for immunotherapy, it can be influenced by many factors. METHODS: A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified. Data for clinical features, gene alternations, signaling pathways and immune signatures was analyzed among negative expression group (TPS < 1%, n = 124), intermediate expression group (1% ≤ TPS < 50%, n = 93), and high expression group (TPS ≥ 50%, n = 38). Clinical outcomes among different expression groups were also evaluated from public database. RESULTS: Firstly, high tumor mutation burden was significantly associated with high PD-L1 expression in these Chinese patients with lung adenocarcinoma. In addition, gene alternations including TP53, PRKDC, KMT2D, TET1 and SETD2 apparently occurred in high PD-L1 expression group. Moreover, pathway analysis showed that mutations involving in DDR pathway, TP53 pathway, cell-cycle pathway and NOTCH pathway were obviously varied among three PD-L1 expression groups. Besides, most of patients in high PD-L1 expression group from TCGA database were determined as high-grade immune subtypes (C2-C4), showing significant higher proportions of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P < 0.0001). Moreover, SETD2 mutation slightly correlated with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90-4.10], P = 0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type group (P < 0.01). CONCLUSIONS: This study illustrated in-depth genomic correlates of PD-L1 expression in Chinese lung adenocarcinoma patients and relevant immune signatures from public database, which might interpret more potential molecular mechanisms for immunotherapy in NSCLC.

Case Report: Durable Complete Response After Combined Immunotherapy Following Resection of Primary Tumor in a Gallbladder Cancer Patient With Distant Metastatic Lymph Nodes of Favorable Immune-Microenvironment.

BACKGROUND: Metastatic gallbladder carcinoma (GBC) is one of the most aggressive malignancies. As GBC is usually diagnosed with distant metastases, only a few patients can receive R0 resection and the relapse rate remains high. Programmed cell death protein 1 (PD-1) blockade therapy has provided encouraging long-term outcomes in a subset of patients in many cancers. However, the data on efficacy of PD-1 blockade in GBC are very limited. CASE PRESENTATION: We herein reported a stage IVB GBC patient with localized primary tumor and distant lymph node metastasis. Except for the unresectable multiple metastatic nodes including distant nodes, a complete resection of primary tumor en bloc with partial segment 4B+5 was performed. Tumor tissues of primary tumor and one metastatic lymph node were collected to perform whole-exome sequencing, RNA-seq, and immunohistochemistry. Low TMB (5.38 muts/Mb), low MSI (<20%), and negative PD-L1 expression (TC0) were observed in the primary tumor. Likewise, low TMB (5.44 muts/Mb), low MSI (<20%), and low PD-L1 expression (TC2) presented in the metastatic lymph node. Besides, low genetic intratumor heterogeneity exhibited between the primary and metastatic tumors in this patient. In contrast to the primary tumor, higher-level CD8+ T cell infiltration was revealed in the tumor microenvironment of the metastatic lymph node. Then, chemo-immunotherapy using S1 and anti-PD-1 antibody pembrolizumab was administrated as the first-line treatment for the residual metastatic nodes. Complete response was achieved after 7 courses and has lasted for 32 months up to present. Additionally, blood samples during treatment were further analyzed for immune repertoire sequencing, showing that several T cell receptor clones in metastatic lymph node were predominant in blood during the combined anti-PD-1 treatment. CONCLUSIONS: Chemo-immunotherapy may provide a potential curative option for the lymph node metastases of gallbladder cancer. The low intratumor heterogeneity and high level of infiltrating CD8+ T-cells in metastatic node might be indispensable to the durable complete response in this patient.

Identification and Validation of 7-lncRNA Signature of Epigenetic Disorders by Comprehensive Epigenetic Analysis.

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

Developing a 5-gene prognostic signature for cervical cancer by integrating mRNA and copy number variations.

BACKGROUND: Cervical cancer is frequently detected gynecological cancer all over the world. This study was designed to develop a prognostic signature for an effective prediction of cervical cancer prognosis. METHODS: Differentially expressed genes (DEGs) were identified based on copy number variation (CNV) data and expression profiles from different databases. A prognostic model was constructed and further optimized by stepwise Akaike information criterion (stepAIC). The model was then evaluated in three groups (training group, test group and validation group). Functional analysis and immune analysis were used to assess the difference between high-risk and low-risk groups. RESULTS: The study developed a 5-gene prognostic model that could accurately classify cervical cancer samples into high-risk and low-risk groups with distinctly different prognosis. Low-risk group exhibited more favorable prognosis and higher immune infiltration than high-risk group. Both univariate and multivariate Cox regression analysis showed that the risk score was an independent risk factor for cervical cancer. CONCLUSIONS: The 5-gene prognostic signature could serve as a predictor for identifying high-risk cervical cancer patients, and provided potential direction for studying the mechanism or drug targets of cervical cancer. The integrated analysis of CNV and mRNA expanded a new perspective for exploring prognostic signatures in cervical cancer.

Understanding the Critical Role of Glycolysis-Related lncRNAs in Lung Adenocarcinoma Based on Three Molecular Subtypes.

BACKGROUND: Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy. METHODS: Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance. RESULTS: Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis. CONCLUSIONS: This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

Two Mn(II) and Zn(II) Coordination Polymers: Aqueous-Phase Detection of Nitroaromatic Explosives and Protective Effect on Atherosclerosis.

Via the solvothermal reaction between Zn(II) or Mn(II) salts and 5-(3,4-dicarboxylphenoxy)nicotinic acid (H3L) ligand, a trifunctional N,O-building block having three diverse kinds of functional groups (O-ether, N-pyridyl and COOH), two new coordination polymers (CPs) could be generated, and their chemical formulae respectively are {[Mn3(L)2(H2O)2]·4H2O} (1) and {[Zn(HL)]·NMP} (2). The complex 2 based on Zn(II) possesses high efficiency of fluorescence quenching for the nitrophenol (2,4,6-trinitrophenol, TNP; 4-nitrophenol, 4-NP; 3-nitrophenol, 3-NP; 2-nitrophenol, 2-NP) in the aqueous solution. Furthermore, the treatment activity of compounds on the atherosclerosis was assessed, and relevant mechanism was investigated. First of all, the ELISA assay was used to measure the content of the inflammatory cytokines released into the plasma. Besides, the levels of the NF-κb signaling pathway in the vascular endothelial cells were measured with real time RT-PCR. The hemolysis test was conducted in this research to measure the biocompatibility of the new compound.