Rapid discrimination of four Salmonella enterica serovars: A performance comparison between benchtop and handheld Raman spectrometers.

Foodborne illnesses, particularly those caused by Salmonella enterica with its extensive array of over 2600 serovars, present a significant public health challenge. Therefore, prompt and precise identification of S. enterica serovars is essential for clinical relevance, which facilitates the understanding of S. enterica transmission routes and the determination of outbreak sources. Classical serotyping methods via molecular subtyping and genomic markers currently suffer from various limitations, such as labour intensiveness, time consumption, etc. Therefore, there is a pressing need to develop new diagnostic techniques. Surface-enhanced Raman spectroscopy (SERS) is a non-invasive diagnostic technique that can generate Raman spectra, based on which rapid and accurate discrimination of bacterial pathogens could be achieved. To generate SERS spectra, a Raman spectrometer is needed to detect and collect signals, which are divided into two types: the expensive benchtop spectrometer and the inexpensive handheld spectrometer. In this study, we compared the performance of two Raman spectrometers to discriminate four closely associated S. enterica serovars, that is, S. enterica subsp. enterica serovar dublin, enteritidis, typhi and typhimurium. Six machine learning algorithms were applied to analyse these SERS spectra. The support vector machine (SVM) model showed the highest accuracy for both handheld (99.97%) and benchtop (99.38%) Raman spectrometers. This study demonstrated that handheld Raman spectrometers achieved similar prediction accuracy as benchtop spectrometers when combined with machine learning models, providing an effective solution for rapid, accurate and cost-effective identification of closely associated S. enterica serovars.

Rapid Detection of Bacterial Pathogens Causing Lower Respiratory Tract Infections via Microfluidic-Chip-Based Loop-Mediated Isothermal Amplification.

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.

Supramolecular interactions between functional saccharide-based ionic liquids and cellulose macromolecules.

Interactions between polysaccharides and ionic liquids (ILs) at the molecular level are essential to elucidate the dissolution and/or plasticization mechanism of polysaccharides. Herein, saccharide-based ILs (SILs) were synthesized, and cellulose membrane was soaked in different SILs to evaluate the interactions between SILs and cellulose macromolecules. The relevant results showed that the addition of SILs into cellulose can effectively reduce the intra- and/or inter-molecular hydrogen bonds of polysaccharides. Glucose-based IL showed the intensest supramolecular interactions with cellulose macromolecules compared to sucrose- and raffinose-based ILs. Two-dimensional correlation and perturbation-correlation moving window Fourier transform infrared techniques were for the first time used to reveal the dynamic variation of the supramolecular interactions between SILs and cellulose macromolecules. Except for the typical HO⋯H interactions of cellulose itself, stronger -Cl⋯HO hydrogen bonding interactions were detected in the specimen of SILs-modified cellulose membranes. Supramolecular interactions of -Cl⋯H, HO⋯H, C-Cl⋯H, and -C=O⋯H between SILs and cellulose macromolecules sequentially responded to the stimuli of temperature. This work provides a new perspective to understanding the interaction mechanism between polysaccharides and ILs, and an avenue to develop the next-generation ILs for dissolving or thermoplasticizing polysaccharide materials.

Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity.

BACKGROUND: Obesity, a condition associated with the development of widespread cardiovascular disease, metabolic disorders, and other health complications, has emerged as a significant global health issue. Oleanolic acid (OA), a pentacyclic triterpenoid compound that is widely distributed in various natural plants, has demonstrated potential anti-inflammatory and anti-atherosclerotic properties. However, the mechanism by which OA fights obesity has not been well studied. METHOD: Network pharmacology was utilized to search for potential targets and pathways of OA against obesity. Molecular docking and molecular dynamics simulations were utilized to validate the interaction of OA with core targets, and an animal model of obesity induced by high-fat eating was then employed to confirm the most central of these targets. RESULTS: The network pharmacology study thoroughly examined 42 important OA targets for the treatment of obesity. The key biological processes (BP), cellular components (CC), and molecular functions (MF) of OA for anti-obesity were identified using GO enrichment analysis, including intracellular receptor signaling, intracellular steroid hormone receptor signaling, chromatin, nucleoplasm, receptor complex, endoplasmic reticulum membrane, and RNA polymerase II transcription Factor Activity. The KEGG/DAVID database enrichment study found that metabolic pathways, PPAR signaling pathways, cancer pathways/PPAR signaling pathways, insulin resistance, and ovarian steroidogenesis all play essential roles in the treatment of obesity and OA. The protein-protein interaction (PPI) network was used to screen nine main targets: PPARG, PPARA, MAPK3, NR3C1, PTGS2, CYP19A1, CNR1, HSD11B1, and AGTR1. Using molecular docking technology, the possible binding mechanism and degree of binding between OA and each important target were validated, demonstrating that OA has a good binding potential with each target. The molecular dynamics simulation's Root Mean Square Deviation (RMSD), and Radius of Gyration (Rg) further demonstrated that OA has strong binding stability with each target. Additional animal studies confirmed the significance of the core target PPARG and the core pathway PPAR signaling pathway in OA anti-obesity. CONCLUSION: Overall, our study utilized a multifaceted approach to investigate the value and mechanisms of OA in treating obesity, thereby providing a novel foundation for the identification and development of natural drug treatments.

Photomechaelectric Nanogenerators with Different Photoisomers and Dipole Units for Harvesting UV Light Energy.

To date, transforming environmental energy into electricity through a non-mechanical way is challenging. Herein, a series of photomechaelectric (PME) polyurethanes containing azobenzene-based photoisomer units and ionic liquid-based dipole units are synthesized, and corresponding PME nanogenerators (PME-NGs) to harvest electricity are fabricated. The dependence of the output performance of PME-NGs on the structure of the polyurethane is evaluated. The results show that the UV light energy can directly transduce into alternating-current (AC) electricity by PME-NGs via a non-mechanical way. The optimal open-circuit voltage and short-circuit current of PME-NGs under UV illumination reach 17.4 V and 696 µA, respectively. After rectification, the AC electricity can be further transformed into direct-current (DC) electricity and stored in a capacitor to serve as a power system to actuate typical microelectronics. The output performance of PME-NGs is closely related to the hard segment content of the PME polyurethane and the radius of counter anions in the dipole units. Kelvin probe force microscopy is used to confirm the existence of the PME effect and the detailed mechanism about the generation of AC electricity in PME-NGs is proposed, referring to the back and forth drift of induced electrons on the two electrodes in contact with the PME polyurethanes.

The emerging significance of mitochondrial targeted strategies in NAFLD treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, ranging from liver steatosis to nonalcoholic steatohepatitis, which ultimately progresses to fibrosis, cirrhosis, and hepatocellular carcinoma. Individuals with NAFLD have a higher risk of developing cardiovascular and extrahepatic cancers. Despite the great progress being made in understanding the pathogenesis and the introduction of new pharmacological targets for NAFLD, no drug or intervention has been accepted for its management. Recent evidence suggests that NAFLD may be a mitochondrial disease, as mitochondrial dysfunction is involved in the pathological processes that lead to NAFLD. In this review, we describe the recent advances in our understanding of the mechanisms associated with mitochondrial dysfunction in NAFLD progression. Moreover, we discuss recent advances in the efficacy of mitochondria-targeted compounds (e.g., Mito-Q, MitoVit-E, MitoTEMPO, SS-31, mitochondrial uncouplers, and mitochondrial pyruvate carrier inhibitors) for treating NAFLD. Furthermore, we present some medications currently being tested in clinical trials for NAFLD treatment, such as exercise, mesenchymal stem cells, bile acids and their analogs, and antidiabetic drugs, with a focus on their efficacy in improving mitochondrial function. Based on this evidence, further investigations into the development of mitochondria-based agents may provide new and promising alternatives for NAFLD management.

Case Report: Double trouble: a rare case of successfully treated Mycoplasma hominis and Pseudomonas aeruginosa co-infection.

Background: Extra-urogenital infections due to Mycoplasma hominis (M. hominis) are rare, particularly co-infection with Pseudomonas aeruginosa (P. aeruginosa). Herein, we report on a patient who was co-infected and successfully treated despite delayed treatment. Case presentation: We reported the case of a 43-year-old man with M. hominis and P. aeruginosa co-infection after a traffic accident. The patient developed a fever and severe infection despite postoperative antimicrobial therapies. The blood culture of wound tissues was positive for P. aeruginosa. Meanwhile, culturing of blood and wound samples showed pinpoint-sized colonies on blood agar plates and fried-egg-type colonies on mycoplasma medium, which were identified as M. hominis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing. Based on antibiotic susceptibility and symptoms, ceftazidime-avibactam and moxifloxacin were administered for P. aeruginosa infection. Meanwhile, after the failure of a series of anti-infective agents, M. hominis and P. aeruginosa co-infection was successfully treated with a minocycline-based regimen and polymyxin B. Conclusion: The co-infection with M. hominis and P. aeruginosa was successfully treated with anti-infective agents despite delayed treatment, providing information for the management of double infection.

Development and Interpretation of a Clinicopathological-Based Model for the Identification of Microsatellite Instability in Colorectal Cancer.

Chemotherapy is not recommended for patients with deficient mismatch repair (dMMR) in colorectal cancer (CRC); therefore, assessing the status of MMR is crucial for the selection of subsequent treatment. This study is aimed at building predictive models to accurately and rapidly identify dMMR. A retrospective analysis was performed at Wuhan Union Hospital between May 2017 and December 2019 based on the clinicopathological data of patients with CRC. The variables were subjected to collinearity, least absolute shrinkage and selection operator (LASSO) regression, and random forest (RF) feature screening analyses. Four sets of machine learning models (extreme gradient boosting (XGBoost), support vector machine (SVM), naive Bayes (NB), and RF) and a conventional logistic regression (LR) model were built for model training and testing. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the developed models. In total, 2279 patients were included in the study and were randomly divided into either the training or test group. Twelve clinicopathological features were incorporated into the development of the predictive models. The area under curve (AUC) values of the five predictive models were 0.8055 for XGBoost, 0.8174 for SVM, 0.7424 for NB, 8584 for RF, and 0.7835 for LR (Delong test, P value < 0.05). The results showed that the RF model exhibited the best recognition ability and outperformed the conventional LR method in identifying dMMR and proficient MMR (pMMR). Our predictive models based on routine clinicopathological data can significantly improve the diagnostic performance of dMMR and pMMR. The four machine learning models outperformed the conventional LR model.

A novel liver zonation phenotype-associated molecular classification of hepatocellular carcinoma.

Background: Liver zonation is a unique phenomenon in which the liver exhibits distinct functions among hepatocytes along the radial axis of the lobule. This phenomenon can cause the sectionalized initiation of several liver diseases, including hepatocellular carcinoma (HCC). However, few studies have explored the zonation features of HCC. Methods: Four single-cell RNA sequencing datasets were used to identify hepatocyte-specific zonation markers. Integrative analysis was then performed with a training RNA-seq cohort (616 HCC samples) and an external validating microarray cohort (285 HCC samples) from the International Cancer Genome Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, and EMBL's European Bioinformatics Institute for clustering using non-negative matrix factorization consensus clustering based on zonation genes. Afterward, we evaluated the prognostic value, clinical characteristics, transcriptome and mutation features, immune infiltration, and immunotherapy response of the HCC subclasses. Results: A total of 94 human hepatocyte-specific zonation markers (39 central markers and 55 portal markers) were identified for the first time. Subsequently, three subgroups of HCC, namely Cluster1, Cluster2, and Cluster3 were identified. Cluster1 exhibited a non-zonational-like signature with the worst prognosis. Cluster2 was intensively associated with a central-like signature and exhibited low immune infiltration and sensitivity toward immune blockade therapy. Cluster3 was intensively correlated with a portal-like signature with the best prognosis. Finally, we identified candidate therapeutic targets and agents for Cluster1 HCC samples. Conclusion: The current study established a novel HCC classification based on liver zonation signature. By classifying HCC into three clusters with non-zonational-like (Cluster1), central-like (Cluster2), and portal-like (Cluster3) features, this study provided new perspectives on the heterogeneity of HCC and shed new light on delivering precision medicine for HCC patients.

RNA methylation regulators contribute to poor prognosis of hepatocellular carcinoma associated with the suppression of bile acid metabolism: a multi-omics analysis.

RNA methylation has been known to promote the initiation and progression of many types of cancer, including hepatocellular carcinoma (HCC). To fully understand the importance of this post-transcriptional modification in HCC, a thorough investigation that combines different patterns of RNA methylation is urgently needed. In this study, we investigated the regulators of the three most common types of RNA methylation: m6A, N1-methyladenosine (m1A) and 5-methylcytosine (m5C). Based on the genomic and proteomic data, we constructed a classifier consisting of seven RNA methylation regulators. This classifier performed well and robustly predicted the prognosis of HCC patients. By analysis using this classifier, we found that the primary bile acid biosynthesis pathway was mostly downregulated in high-risk HCC patients. Furthermore, we found that the gene expression patterns regulated by several bile acids were similar to those regulated by some well-defined anti-tumor compounds, indicating that bile acid metabolism plays a crucial role in the progression of HCC, and the related metabolites can be used as the potential agents for HCC treatments. Moreover, our study revealed a crosstalk between RNA methylation and bile acid regulators, demonstrating a novel mechanism of the downregulation of bile acid metabolism in HCC and providing new insights into how RNA methylation regulators affect the oncogenesis of HCC.

Catheter-related infections caused by Mycobacterium abscessus in a patient with motor neurone disease: A case report.

BACKGROUND: Mycobacterium abscessus (M. abscessus) is a rapidly growing mycobacterium and ubiquitous in the environment, which infrequently causes disease in humans. However, it can cause cutaneous or respiratory infections among immunocompromised hosts. Due to the resistance to most antibiotics, the pathogen is formidable and difficult-to-treat. CASE SUMMARY: Here, we present a case of catheter-related M. abscessus infections in a patient with motor neurone disease. Catheter and peripheral blood cultures of the patient showed positive results during Gram staining and acid-fast staining. The alarm time of catheter blood culture was 10.6 h earlier than that of peripheral blood. After removal of the peripherally inserted central catheter, secretion and catheter blood culture were positive. M. abscessus was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and 16S rDNA sequencing. CONCLUSION: For catheter-related M. abscessus infection, rapid diagnosis and timely and adequate antimicrobial therapy are crucial.

Development and validation of a prognostic scoring system for patients with colorectal cancer hepato-pulmonary metastasis: a retrospective study.

BACKGROUND: Hepato-pulmonary metastasis of colorectal cancer (CRC) is a rare disease with poor prognosis. This study aims to establish a highly efficient nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer hepato-pulmonary metastasis (CRCHPM). METHODS: We retrospectively analyzed the data of patients with CRCHPM from SEER database and Wuhan Union Hospital Cancer Center (WUHCC). A total of 1250 CRCHPM patients were randomly assigned to the training, internal validation, and external validation cohorts from 2010 to 2016.Univariate and multivariate cox analysis were performed to identify independent clinicopathological predictors of OS and CSS, and a nomogram was constructed to predict OS and CSS in CRCHPM patients. RESULTS: A nomogram of OS was constructed based on seven independent predictors of age, degree of differentiation, T stage, chemotherapy, number of lsampled lymph nodes, number of positive lymph nodes, and tumor size. Nomogram showed favorable sensitivity in predicting OS at 1, 3 and 5 years, with area under the receiver operating characteristic curve (AUROC) values of 0.802, 0.759 and 0.752 in the training cohort;0.814, 0.769 and 0.716 in the internal validation cohort;0.778, 0.756 and 0.753 in the external validation cohort, respectively. A nomogram of CSS was constructed based on three independent predictors of T stage, chemotherapy, and tumor size. The AUROC values of 1, 3 and 5 years were 0.709,0.588,0.686 in the training cohort; 0.751, 0.648,0.666 in the internal validation cohort;0.781,0.588,0.645 in the external validation cohort, respectively. Calibration curves, Concordance index (C-index), and decision curve analysis (DCA) results revealed that using our model to predict OS and CSS is more efficient than other single clinicopathological characteristics. CONCLUSION: A nomogram of OS and CSS based on clinicopathological characteristics can be conveniently used to predict the prognosis of CRCHPM patients.

The Prognostic Significance of RIMKLB and Related Immune Infiltrates in Colorectal Cancers.

RimK-like family member B (RIMKLB) is an enzyme that post-translationally modulates ribosomal protein S6, which can affect the development of immune cells. Some studies have suggested its role in tumor progression. However, the relationships among RIMKLB expression, survival outcomes, and tumor-infiltrating immune cells (TIICs) in colorectal cancer (CRC) are still unknown. Therefore, we analyzed RIMKLB expression levels in CRC and normal tissues and investigated the correlations between RIMKLB and TIICs as well as the impact of RIMKLB expression on clinical prognosis in CRC using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and UALCAN databases. Enrichment analysis was conducted with the cluster Profiler package in R software to explore the RIMKLB-related biological processes involved in CRC. The RIMKLB expression was significantly decreased in CRC compared to normal tissues, and correlated with histology, stage, lymphatic metastasis, and tumor status (p < 0.05). Patients with CRC with high expression of RIMKLB showed poorer overall survival (OS) (HR = 2.5,p = 0.00,042), and inferior disease-free survival (DFS) (HR = 1.9,p = 0.19) than those with low expression of RIMKLB. TIMER analysis indicated that RIMKLB transcription was closely related with several TIICs, including CD4+ and CD8+ T cells, B cells, tumor-associated macrophages (TAMs), monocytes, neutrophils, natural killer cells, dendritic cells, and subsets of T cells. Moreover, the expression of RIMKLB showed significant positive correlations with infiltrating levels of PD1 (r = 0.223, p = 1.31e-06; r = 0.249, p = 1.25e-03), PDL1 (r = 0.223, p = 6.03e-07; r = 0.41, p = 5.45e-08), and CTLA4 (r = 0.325, p = 9.68e-13; r = 0.41, p = 5.45e-08) in colon and rectum cancer, respectively. Enrichment analysis showed that the RIMKLB expression was positively related to extracellular matrix and immune inflammation-related pathways. In conclusion, RIMKLB expression is associated with survival outcomes and TIICs levels in patients with CRC, and therefore, might be a potential novel prognostic biomarker that reflects the immune infiltration status.

Transcriptome expression profiles reveal response mechanisms to drought and drought-stress mitigation mechanisms by exogenous glycine betaine in maize.

Drought stress is one of the major abiotic stresses that limit growth, development and yield of maize crops. To better understand the responses of maize inbred lines with different levels of drought resistance and the molecular mechanism of exogenous glycine betaine (GB) in alleviating drought stress, the responses of two maize inbred lines to drought stress and to the stress-mitigating effects of exogenous GB were investigated. Seedling morphology, physiological and biochemical indexes, root cell morphology and root transcriptome expression profiles were compared between a drought-tolerant inbred line Chang 7-2 and drought-sensitive inbred line TS141. Plants of both lines were subjected to treatments of drought stress alone and drought stress with application of exogenous GB. The results showed that with the increase of drought treatment time, the growth and development of TS141 were inhibited, while those of Chang 7-2 were not significantly different from those of the control (no drought stress and GB). Compared with the corresponding data of the drought-stress group, every index measured from the two inbred lines indicated mitigating effects from exogenous GB, and TS141 produced stronger mitigating responses due to the GB. Transcriptome analysis showed that 562 differentially expressed genes (DEGs) were up-regulated and 824 DEGs were down-regulated in both inbred lines under drought stress. Due to the exogenous GB, 1061 DEGs were up-regulated and 424 DEGs were down-regulated in both lines. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify 10 DEGs screened from the different treatments. These results showed that the expression of 9 DEGs were basically consistent with their respective transcriptome expression profiles. The results of this study provide models of potential mechanisms of drought tolerance in maize as well as potential mechanisms of how exogenous GB may regulate drought tolerance.

808 nm Near-Infrared Light-Triggered Payload Release from Green Light-Responsive Donor-Acceptor Stenhouse Adducts Polymer-Coated Upconversion Nanoparticles.

Owing to deep activation in biotissues and enhanced targeting efficiency, developing photoresponsive polymer-upconversion nanoparticles (PP-UCNPs) nanovectors has witnessed rapid growth in the past decade. However, up to date, all developed nanovectors require high-order photon processes to initiate the release of cargos. The photodamage caused by high-power near-infrared laser light may be a critical obstacle to their clinical application. Here, for the first time, by leveraging absorption-emission spectral matching between donor-acceptor Stenhouse adducts (DASA) PP and UCNPs (λex , 808 nm) in the green region (≈530 nm), the designed nanovector is capable of releasing cargos at a low-power 808 nm excitation (0.2 W). Considering the high molar absorptivity, biobenign, and synthetic tunability of DASA, DASA PP can be utilized as an up-and-coming candidate to design and synthesize the next generation of upconversion nanovectors without photodamage.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Serum Tumor Markers Combined With Clinicopathological Characteristics for Predicting MMR and KRAS Status in 2279 Chinese Colorectal Cancer Patients: A Retrospective Analysis.

Although serum tumor markers (STMs), clinicopathological characteristics and the status of KRAS and MMR play an important role in optimizing the treatment and prognosis of colorectal cancer, their interrelationships remain largely unknown. A retrospective analysis of 2279 patients who tested for KRAS and MMR status, and STM measurements prior to treatment over the past four years was conducted. Of the 784 patients tested for KRAS and 2279 patients tested for MMR status, KRAS mutations and dMMR were identified in 276 patients (35.20%) and 177 patients (7.77%), respectively. Logistic regression analysis demonstrated that right colon, well and moderate differentiation and negative CA19-9 were independent predictors for KRAS mutations. The ROC curve yielded an AUC of 0.609 through the combination of these three factors. Age < 65 was an independent predictive factor for dMMR, along with tumor size > 4.6 cm, right colon, poor differentiation, harvested lymph nodes ≥ 22, no lymph node metastasis, no perineural invasion, negative CEA and positive CA72-4. When the nine criteria were used together, the AUC was 0.849. In summary, both STMs and clinicopathological characteristics were found to be significantly associated with the status of KRAS and MMR. The combination of these two factors possessed a strong predictive power for KRAS mutations and dMMR among CRC patients.

Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-associated deaths worldwide. Despite great progress in early diagnosis and multidisciplinary tumor management, the long-term prognosis of HCC remains poor. Currently, metabolic reprogramming during tumor development is widely observed to support rapid growth and proliferation of cancer cells, and several metabolic targets that could be used as cancer biomarkers have been identified. The liver and mitochondria are the two centers of human metabolism at the whole organism and cellular levels, respectively. Thus, identification of prognostic biomarkers based on mitochondrial-related genes (Mito-RGs)-the coding-genes of proteins located in the mitochondria-that reflect metabolic changes associated with HCC could lead to better interventions for HCC patients. In the present study, we used HCC data from The Cancer Genome Atlas (TCGA) database to construct a classifier containing 10 Mito-RGs (ACOT7, ADPRHL2, ATAD3A, BSG, FAM72A, PDK3, PDSS1, RAD51C, TOMM34, and TRMU) for predicting the prognosis of HCC by using 10-fold Least Absolute Shrinkage and Selection Operation (LASSO) cross-validation Cox regression. Based on the risk score calculated by the classifier, the samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), t-distributed stochastic neighbor embedding (t-SNE), and consensus clusterPlus algorithms were used to identify metabolic pathways that were significantly different between the high- and low-risk groups. We further investigated the relationship between metabolic status and infiltration of immune cells into HCC tumor samples by using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm combined with the Tumor Immune Estimation Resource (TIMER) database. Our results showed that the classifier based on Mito-RGs could act as an independent biomarker for predicting survival of HCC patients. Repression of primary bile acid biosynthesis plays a vital role in the development and poor prognosis of HCC, which provides a potential approach to treatment. Our study revealed cross-talk between bile acid and infiltration of tumors by immune cells, which may provide novel insight into immunotherapy of HCC. Furthermore, our research may provide a novel method for HCC metabolic therapy based on modulation of mitochondrial function.

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

Application of endoscopic technique in completely occluded anastomosis with anastomotic separation after radical resection of colon cancer: a case report and literature review.

BACKGROUND: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations. CASE PRESENTATION: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed. CONCLUSIONS: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.