Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.

OBJECTIVE: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM. METHODS: An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies. RESULTS: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice. CONCLUSIONS: NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

Navigating the immune landscape with plasma cells: A pan-cancer signature for precision immunotherapy.

Immunotherapy has revolutionized cancer treatment; however, predicting patient response remains a significant challenge. Our study identified a novel plasma cell signature, Plasma cell.Sig, through a pan-cancer single-cell RNA sequencing analysis, which predicts patient outcomes to immunotherapy with remarkable accuracy. The signature was developed using rigorous machine learning algorithms and validated across multiple cohorts, demonstrating superior predictive power with an area under the curve (AUC) exceeding 0.7. Notably, the low-risk group, as classified by Plasma cell.Sig, exhibited enriched immune cell infiltration and heightened tumor immunogenicity, indicating an enhanced responsiveness to immunotherapy. Conversely, the high-risk group showed reduced immune activity and potential mechanisms of immune evasion. These findings not only enhance understanding of the intrinsic and extrinsic immune landscapes within the tumor microenvironment but also pave the way for more precise, biomarker-guided immunotherapy approaches in oncology.

Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.

Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.

Research status and hotspots of tight junctions and colorectal cancer: A bibliometric and visualization analysis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Over the past two decades, numerous researchers have provided important evidence regarding the role of tight junction (TJ) proteins in the occurrence and progression of CRC. The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed. Despite the large number of publications in this field, a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed. AIM: To analyze research on TJs and CRC, summarize the field's history and current status, and predict future research directions. METHODS: We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023. We used bibliometrics to analyze the data of these papers, such as the authors, countries, institutions, and references. Co-authorship, co-citation, and co-occurrence analyses were the main methods of analysis. CiteSpace and VOSviewer were used to visualize the results. RESULTS: A total of 205 studies were ultimately identified. The number of publications on this topic has steadily increased since 2007. China and the United States have made the largest contributions to this field. Anticancer Research was the most prolific journal, publishing 8 articles, while the journal Oncogene had the highest average citation rate (68.33). Professor Dhawan P was the most prolific and cited author in this field. Co-occurrence analysis of keywords revealed that "tight junction protein expression", "colorectal cancer", "intestinal microbiota", and "inflammatory bowel disease" had the highest frequency of occurrence, revealing the research hotspots and trends in this field. CONCLUSION: This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC, providing valuable research perspectives and future directions for studying the connection between the two. It is recommended to focus on emerging research hotspots, such as the correlations among intestinal microbiota, inflammatory bowel disease, TJ protein expression, and CRC.

Intestinal epithelial Cldn-7 regulates intestinal inflammation by altering the gut microbiota.

BACKGROUND AND AIM: Tight junctions maintain gut homeostasis by forming a physical barrier that protects the gut from invasion by microbiota. Cldn-7 is an important component involved in this protection, but the relationship between Cldn-7, intestinal inflammation, and gut microbiota has not been clarified. Here, we hypothesize that Cldn-7 depletion affects intestinal inflammation by altering the gut microbiota. METHODS: Based on the induced intestinal condition of Cldn-7 knockout mice (Cldn7fl/fl;villin-CreaERT2), we established the intestinal flora depletion model and colitis model by antibiotic drinking and feeding with dextran sodium sulfate (DSS). The environment of Cldn-7 gene deletion mice was changed by co-housing experiment. AB-PAS staining and Muc2 were used to detect the effect of co-housing and Cldn-7 deficiency on the mucus layer after flora depletion. qRT-PCR was used to detect the expression of intestinal inflammatory factors and AMPs in mice. Feces were collected and proportions of microbiota were analyzed by 16 S rRNA amplicon sequencing. RESULTS: Mice in the co-housing experiment had altered intestinal microbiota, including diversity, composition, and functional prediction, compared to controls. Intestinal inflammation was restored to some extent following altered intestinal microbiota. The intestinal inflammation caused by Cldn-7 deficiency and susceptibility to DSS could be reduced after antibiotic administration compared to controls, in terms of phenotype, pathological changes, inflammatory factors, mucus barrier, and expression of AMPs. CONCLUSIONS: In analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal disruption of Cldn-7, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. Cldn-7might therefore be an important mediator of host-microbiome interactions. Our research has revealed that Cldn-7 plays an indispensable role in maintaining intestinal homeostasis by regulating the gut microbiota and impacting intestinal inflammation. These findings provide new insights into the pathogenesis of ulcerative colitis.

Association between flavonoid intake and rheumatoid arthritis among US adults.

Basic research shows that flavonoids have anti-inflammatory effects that influence rheumatoid arthritis (RA) in rats. Investigating potential dietary interventions for RA helps prevent the onset and progression of the disease. Clinical evidence on the association of flavonoid and subclass intake with RA is lacking. Using three survey cycles of 2007-2008, 2009-2010, and 2017-2018 from the National Health and Nutrition Survey and the United States Department of Agriculture's Food and Nutrient Database for Dietary Studies (FNDDS), we analyzed 7,419 American adults (≥20 years old). The values of flavonoid and subclass intake were calculated using FNDDS. The status questions for self-reported RA were from the NHANES codebook. Weighted analyses, revealed that among the 7,419 participants included in this study (mean age of 44.69 years [standard error, 0.40] and 3,584 [48.31%] were female), 408 met the classification criteria for RA. According to the multivariable logistic regression model, compared with the risk of RA in the first quartile (Q1), the risks of RA in the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4) were lower (Q2: OR=0.55, 95% CI: 0.38-0.80; Q3: OR=0.66, 95% CI: 0.44-0.97; Q4: OR=0.64, 95% CI: 0.46-0.89; trend: P=.03). The association between total flavonoids and RA remained significant after full consideration of confounding factors. With regard to the subclasses of flavonoids, high flavanones intake was associated with low RA prevalence in Model 3 (Q3: OR= 0.60, 95% CI:0.39-0.92; Q4: OR = 0.56, 95% CI: 0.32-0.99, trend: P=.02), but no such association was found in the other subclasses. Total flavonoids intake protected against RA, and the risk of developing RA decreased significantly with increasing intake of total flavonoids. Total flavonoids and flavanones were significantly associated with reduced RA risk for the American adult population. We highlighted the importance of employing diverse methodologies to assess the health effects of flavonoids.

Titanium Alloy Materials with Very High Cycle Fatigue: A Review.

As the reliability and lifespan requirements of modern equipment continues to escalate, the problems with very high cycle fatigue (VHCF) has obtained increasingly widespread attention, becoming a hot topic in fatigue research. Titanium alloys, which are the most extensively used metal materials in the modern aerospace industry, are particularly prone to VHCF issues. The present study systematically reviewed and summarized the latest (since 2010) developments in VHCF research on titanium alloy, with special focus on the (i) experimental methods, (ii) macroscopic and microscopic characteristics of the fatigue fractures, and (iii) construction of fatigue fracture models. More specifically, the review addresses the technological approaches that were used, mechanisms of fatigue crack initiation, features of the S-N curves and Goodman diagrams, and impact of various factors (such as processing, temperature, and corrosion). In addition, it elucidates the damage mechanisms, evolution, and modeling of VHCF in titanium alloys, thereby improving the understanding of VHCF patterns in titanium alloys and highlighting the current challenges in VHCF research.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

Identifying molecular subtypes and tumor microenvironment infiltration signatures in kidney renal clear cell carcinoma based on stemness-associated disulfidptosis genes by integrating machine learning, single-cell analyses and experimental validation.

Clear cell renal cell carcinoma (ccRCC) is an aggressive malignant tumor. Disulfidptosis is a new programmed cell death mechanism, which is characterized by the abnormal accumulation of intracellular disulfides that are highly toxic to cells. However, the contribution of disulfidptosis to ccRCC progression has not been fully clarified. In this study, two different molecular subtypes related to disulfidptosis were identified in ccRCC patients by the non-negative matrix factorization (NMF) algorithm. The cluster 1 was characterized by a worse prognosis and higher mRNAsi levels. Then, difference analysis and weighted gene co-expression network analysis (WGCNA) were conducted to search modular genes that are highly associated with tumor stemness and tumor microenvironment. Subsequently, a SADG signature containing nine genes was constructed stepwise by WGCNA and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The high-risk score group had a worse outcome, and immune regulation and metabolic signatures might be responsible for cancer progression in the high-risk group. After that, a predictive nomogram was constructed, and the predicting power of the risk model was verified using inter and three independent external validation datasets. Nine SADGs were shown to significantly correlate with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI) and immune checkpoint. In addition, based on the single-cell RNA sequencing dataset (GSE139555), the distribution and expression of nine hub genes in various types of immune cells were analyzed. Finally, the expression level of the nine genes was verified in clinical samples by qRT-PCR.

The role of intestinal microecology in inflammatory bowel disease and colorectal cancer: A review.

Intestinal microecology is a dominant and complex microecological system in human body. Generally, intestinal microecosystem consists of normal symbiotic flora and its living environment (including intestinal epithelial tissue and intestinal mucosal immune system). Commensal flora is the core component of microecology. Both structures of intestinal mucosa and functions of immune system are essential to maintain homeostasis of intestinal microecosystem. Under normal conditions, intestinal microorganisms and intestinal mucosa coordinate with each other to promote host immunity. When certain factors in the intestine are altered, such as disruption of the intestinal barrier causing dysbiosis of the intestinal flora, the immune system of the host intestinal mucosa makes a series of responses, which leads to the development of intestinal inflammation and promotes colorectal cancer. In this review, to further understand the relationship between intestinal microecology and intestinal diseases, we systematically elaborate the composition of the intestinal mucosal immune system, analyze the relationship between intestinal flora and mucosal immune system, and the role of intestinal flora on intestinal inflammatory diseases and colorectal cancer.

Whole-joint histogram analysis of different models of diffusion weighted imaging in evaluating disease activity of axial spondyloarthritis.

OBJECTIVES: To assess whole-joint histogram analysis of mono-exponential and bi-exponential diffusion weighted and diffusion kurtosis imaging in evaluating disease activity of axial spondyloarthritis (axSpA). METHODS: A total of 82 patients with axSpA who underwent both DKI and multi b diffusion weighted imaging of the sacroiliac joints were divided into active and inactive disease groups based on clinical activity indices. Another 17 patients with nonspecific low back pain were included as a control group. The SPARCC scoring system was used to assess the level of sacroiliac joint bone marrow edema. Histogram parameters of apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), pseudodiffusion coefficient (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated. Regions of interest were placed covering the entire sacroiliac joint. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of imaging parameters in distinguishing different groups. Regression analysis was applied to determine the correlation between imaging parameters and clinical activity indices. RESULTS: All of the histogram parameters distinguished the active from inactive groups with a low area under the curve (AUC) (max AUCs≤0.71), while the SPARCC score failed to differentiate the two groups (p = 0.08). MD, MK, D, D*, and ADC showed good performance in differentiating active and inactive from control groups (max AUC = 0. 81 ~ 0.98). f50 differentiated the active from control groups with an AUC of 0.72, significantly lower than the maximum AUC for MD, MK, D, ADC, and SPARCC score (all p < 0.05). The max AUC of MD in differentiating inactive from control groups was significantly higher than that of D* and the SPARCC score. MD, D, D*, f, and ADC were positively correlated with BASDAI, while MK was negatively correlated with BASDAI. Only MD was positively correlated with hsCRP. CONCLUSIONS: Whole-joint histogram analysis of mono-exponential, bi-exponential diffusion weighted, and diffusion kurtosis imaging showed good diagnostic performance in differentiating active and inactive axSpA from patients with non-specific back pain. All the imaging parameters were correlated with BASDAI except for SPARCC score. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA. ADVANCES IN KNOWLEDGE: 1. No significant difference was found between the three models of diffusion weighted imaging in evaluating disease activity of axial spondyloarthritis.2. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA.

Clinical outcomes of parenchymal-sparing versus anatomic resection for colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy. METHODS: A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases. RESULTS: Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001). CONCLUSION: Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence. TRIAL REGISTRATION: PROSPERO registration number: CRD42023445332.

Immunological factors in cirrhosis diseases from a bibliometric point of view.

BACKGROUND: Cirrhosis results from persistent liver injury that leads to liver fibrosis. Immunological factors play important regulatory roles in the development and progression of cirrhosis. Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study. To date, there are no bibliometric studies on the role of immunological factors in cirrhosis. AIM: To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis. METHODS: We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7, 2022. The search strategy was TS = ((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis) AND (Immunologic* Factor* OR Immune Factor* OR Immunomodulator* OR Biological Response Modifier* OR Biomodulator*)). Only original articles and reviews were included. A total of 2873 publications were analyzed using indicators of publication and citation metrics, countries, institutes, authors, journals, references, and keywords by CiteSpace and VOSviewer. RESULTS: A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals. In the past 20 years, the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development. The United States (781/27.18%), China (538/18.73%), and Germany (300/10.44%) were the leading countries in this field. Most of the top 10 authors were from the United States (4) and Germany (3), with Gershwin ME contributing the most related articles (42). World Journal of Gastroenterology was the most productive journal, whereas Hepatology was the most co-cited journal. Current research hotspots regarding immunological factors in cirrhosis include fibrosis, cirrhosis, inflammation, liver fibrosis, expression, hepatocellular carcinoma, activation, primary biliary cirrhosis, disease, and hepatic stellate cells. Burst keywords (e.g., epidemiology, gut microbiota, and pathways) represent research frontiers that have attracted the interest of researchers in recent years. CONCLUSION: This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis, providing new ideas for promoting scientific research and clinical applications.

Modulating the Oxygen Reduction Reaction Performance via Precisely Tuned Reactive Sites in Porphyrin-Based Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as promising electrocatalysts due to their controllable architectures, highly exposed molecular active sites, and ordered structures. In this study, a series of porphyrin-based COFs (TAPP-x-COF) with various transition metals (Co, Ni, Fe) were synthesized via a facile post-metallization strategy under solvothermal synthesis. The resulting porphyrin-based COFs showed oxygen reduction reaction (ORR) activity with a trend in Co > Fe > Ni. Among them, TAPP-Co-COF exhibited the best ORR activity (E1/2 = 0.66 V and jL = 4.82 mA cm-2) in alkaline media, which is comparable to those of Pt/C under the same conditions. Furthermore, TAPP-Co-COF was employed as a cathode in a Zn-air battery, demonstrating a high power density of 103.73 mW cm-2 and robust cycling stability. This work presents a simple method for using COFs as a smart platform to fabricate efficient electrocatalysts.

Pivotal role of the B12-core in the structural evolution of B52-B64 clusters.

An icosahedral B12 cage is a basic building block of various boron allotropes, and it also plays a vital role in augmenting the stability of fullerene-like boron nanoclusters. However, the evolution of compact core-shell structures is still a puzzle. Using a genetic algorithm combined with density functional theory calculations, we have performed a global search for the lowest-energy structures of Bn clusters with n = 52-64, which reveals that bilayer and core-shell motifs frequently alternate as the ground state. Their structural stability is assessed, and the competition mechanism between various patterns is also elucidated. More interestingly, an unprecedented icosahedral B12-core half-covered structure is identified at B58, which bridges the gap between the smallest core-shell B4@B42 and the complete core-shell B12@B84 cluster. Our findings provide valuable insights into the bonding pattern and growth behavior of medium-sized boron clusters, which facilitate the experimental synthesis of boron nanostructures.

Development of an immune-related gene prognostic risk model and identification of an immune infiltration signature in the tumor microenvironment of colon cancer.

BACKGROUND: Colon cancer is a common and highly malignant tumor. Its incidence is increasing rapidly with poor prognosis. At present, immunotherapy is a rapidly developing treatment for colon cancer. The aim of this study was to construct a prognostic risk model based on immune genes for early diagnosis and accurate prognostic prediction of colon cancer. METHODS: Transcriptome data and clinical data were downloaded from the cancer Genome Atlas database. Immunity genes were obtained from ImmPort database. The differentially expressed transcription factors (TFs) were obtained from Cistrome database. Differentially expressed (DE) immune genes were identified in 473 cases of colon cancer and 41 cases of normal adjacent tissues. An immune-related prognostic model of colon cancer was established and its clinical applicability was verified. Among 318 tumor-related transcription factors, differentially expressed transcription factors were finally obtained, and a regulatory network was constructed according to the up-down regulatory relationship. RESULTS: A total of 477 DE immune genes (180 up-regulated and 297 down-regulated) were detected. We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. The model was proved to be an independent prognostic variable with good prognostic ability. A total of 68 DE TFs (40 up-regulated and 23 down-regulated) were obtained. The regulation network between TF and immune genes was plotted by using TF as source node and immune genes as target node. In addition, Macrophage, Myeloid Dendritic cell and CD4+ T cell increased with the increase of risk score. CONCLUSION: We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. This model can be used as a tool variable to predict the prognosis of colon cancer.

Structural and photoelectron spectroscopic study on the heterotrinuclear nickel-titanium dioxide carbonyl complexes Ni2TiO2(CO) n - (n = 2-4).

Herein, the configurations and intrinsic electronic properties of heteronuclear transition metal dioxide carbonyl anions Ni2TiO2(CO) n - (n = 2-4) in the gas phase were investigated using mass spectrometry coupled anionic photoelectron spectroscopy, ab initio calculations, and simulated density-of-state (DOS) spectra. The results clearly show that the binding of electrons is enhanced by the addition of CO. The ground state structures of Ni2TiO2(CO) n - (n = 2-4) are characterized to show that three transition metal atoms (one Ti atom and two Ni atoms) forming a quasi-line is favored. The interaction between Ni and C becomes weaker as the cluster size increases. The natural electron configuration shows that the extra electron is enriched on O atoms attached to Ti, and there is strong interaction between Ti and O atoms. This work gives significant insight into the configuration and electronic structures of nickel-titanium dioxide carbonyl anions, which has potential application in adsorption of carbon monoxide on the surfaces/interfaces of alloys.

Pyroptosis-related lncRNAs: A novel prognosis signature of colorectal cancer.

Pyroptosis is a newly discovered programmed cell death mechanism involved in tumorigenesis. Long non-coding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). However, the potential role of pyroptosis-related lncRNAs (PRLs) in CRC remains unelucidated. Therefore, we retrieved transcriptomic data of CRC patients from The Cancer Genome Atlas (TCGA). With the use of univariate and multivariate Cox proportional hazards regression models and the random forest algorithm, a new risk model was constructed based on eight PRLs: Z99289.2, FENDRR, CCDC144NL-ASL, TEX41, MNX1-AS1, NKILA, LINC02798, and LINC02381. Then, according to the Kaplan-Meier plots, the relationship of PRLs with the survival of CRC patients was explored and validated with our risk model in external datasets (Gene Expression Omnibus (GEO) databases; GEO17536, n = 177, and GSE161158, n = 250). To improve its clinical utility, a nomogram combining PRLs that could predict the clinical outcome of CRC patients was established. A full-spectrum immune landscape of CRC patients mediated by PRLs could be described. The PRLs were stratified into two molecular subtypes involved in immune modulators, immune infiltration of tumor immune microenvironment, and inflammatory pathways. Afterward, Tumor Immune Dysfunction and Exclusion (TIDE) and microsatellite instability (MSI) scores were analyzed. Three independent methods were applied to predict PRL-related sensitivity to chemotherapeutic drugs. Our comprehensive analysis of PRLs in CRC patients demonstrates a potential role of PRLs in predicting response to treatment and prognosis of CRC patients, which may provide a better understanding of molecular mechanisms underlying CRC pathogenesis and facilitate the development of effective immunotherapy.

The complete chloroplast genome of Crepis rigescens (Cichorioideae), a traditional Chinese medicinal plant.

Crepis rigescens, Diels 1921 is a traditional Chinese medicinal plant of Cichorioideae, which contains many chemicals, such as friedelin, ß-sitosterol, stigmasterol, chlorogenic acid, and flavonoids, and so on, which has the characteristics of high medicinal value and small side effect. Crepis rigescens was used as folk medicines for anti-bacterial, and anti-oxidation, which also had a potential curative effect in preventing cardiovascular disease and anti-tumor. Illumina paired-end reads data were used to assemble the complete chloroplast (cp) genome. 14,425,796 raw paired-end reads and the length distribution in 124,685 bp, including a large single copy (LSC) region of 82,924 bp, a small single copy (SSC) region of 18,150 bp, and a pair of inverted repeat (IRs) regions of 25,128 bp. Besides, 10 protein-coding genes (PCGs) genes and 6 tRNAs genes possess a single intron, while clpP and ycf3 have a couple of introns. Based on the concatenated coding sequences of cp PCGs, the phylogenetic analysis showed that C. rigescens and Hypochaeris radicata (MH746729) are closely related to each other within the family Cichorioideae.