CellGO: a novel deep learning-based framework and webserver for cell-type-specific gene function interpretation.

Interpreting the function of genes and gene sets identified from omics experiments remains a challenge, as current pathway analysis tools often fail to consider the critical biological context, such as tissue or cell-type specificity. To address this limitation, we introduced CellGO. CellGO tackles this challenge by leveraging the visible neural network (VNN) and single-cell gene expressions to mimic cell-type-specific signaling propagation along the Gene Ontology tree within a cell. This design enables a novel scoring system to calculate the cell-type-specific gene-pathway paired active scores, based on which, CellGO is able to identify cell-type-specific active pathways associated with single genes. In addition, by aggregating the activities of single genes, CellGO extends its capability to identify cell-type-specific active pathways for a given gene set. To enhance biological interpretation, CellGO offers additional features, including the identification of significantly active cell types and driver genes and community analysis of pathways. To validate its performance, CellGO was assessed using a gene set comprising mixed cell-type markers, confirming its ability to discern active pathways across distinct cell types. Subsequent benchmarking analyses demonstrated CellGO's superiority in effectively identifying cell types and their corresponding cell-type-specific pathways affected by gene knockouts, using either single genes or sets of genes differentially expressed between knockout and control samples. Moreover, CellGO demonstrated its ability to infer cell-type-specific pathogenesis for disease risk genes. Accessible as a Python package, CellGO also provides a user-friendly web interface, making it a versatile and accessible tool for researchers in the field.

Adaptive Laboratory Evolution of Probiotics toward Oxidative Stress Using a Microfluidic-Based Platform.

Adaptive laboratory evolution (ALE) can be used to make bacteria less susceptible to oxidative stress. An alternative to large batch scale ALE cultures is to use microfluidic platforms, which are often more economical and more efficient. Microfluidic ALE platforms have shown promise, but many have suffered from subpar cell passaging mechanisms and poor spatial definition. A new approach is presented using a microfluidic Evolution on a Chip (EVoc) design which progressively drives microbial cells from areas of lower H2O2 concentration to areas of higher concentration. Prolonged exposure, up to 72 h, revealed the survival of adaptive strains of Lacticaseibacillus rhamnosus GG, a beneficial probiotic often included in food products. After performing ALE on this microfluidic platform, the bacteria persisted under high H2O2 concentrations in repeated trials. After two progressive exposures, the ability of L. rhamnosus to grow in the presence of H2O2 increased from 1 mm H2O2 after a lag time of 31 h to 1 mm after 21 h, 2 mm after 28 h, and 3 mm after 42 h. The adaptive strains have different morphology, and gene expression compared to wild type, and genome sequencing revealed a potentially meaningful single nucleotide mutation in the protein omega-amidase.

Serum deprivation protein response intervenes in the proliferation, motility, and extracellular matrix production in keloid fibroblasts by blocking the amplification of TGF-ß1/SMAD signal cascade via ERK1/2.

Keloid formation has been linked to abnormal fibroblast function, such as excessive proliferation and extracellular matrix (ECM) production. Serum deprivation protein response (SDPR) is a crucial regulator of cellular function under diverse pathological conditions, yet its role in keloid formation remains unknown. The current work investigated the function of SDPR in regulating the proliferation, motility, and ECM production of keloid fibroblasts (KFs), as well as to decipher the mechanisms involved. Analysis of RNA sequencing data from the GEO database demonstrated significant down-regulation of SDPR in KF compared to normal fibroblasts (NFs). This down-regulation was also observed in clinical keloid specimens and isolated KFs. Overexpression of SDPR suppressed the proliferation, motility, and ECM production of KFs, while depletion of SDPR exacerbated the enhancing impact of TGF-ß1 on the proliferation, motility, and ECM production of NFs. Mechanistic studies revealed that SDPR overexpression repressed TGF-ß/Smad signal cascade activation in KFs along with decreased levels of phosphorylated Samd2/3, while SDPR depletion exacerbated TGF-ß/Smad activation in TGF-ß1-stimulated NFs. SDPR overexpression also repressed ERK1/2 activation in KFs, while SDPR depletion exacerbated ERK1/2 activation in TGF-ß1-stimulated NFs. Inhibition of ERK1/2 abolished SDPR-depletion-induced TGF-ß1/Smad activation, cell proliferation, motility, and ECM production in NFs. In conclusion, SDPR represses the proliferation, motility, and ECM production in KFs by blocking the TGF-ß1/Smad pathway in an ERK1/2-dependent manner. The findings highlight the role of SDPR in regulating abnormal behaviors of fibroblasts associated with keloid formation and suggest it as a potential target for anti-keloid therapy development.

ZFHX3 methylation in peripheral blood monocytes as a potential biomarker for pancreatic cancer detection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers. OBJECTIVE: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC. METHODS: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel. RESULTS: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71). CONCLUSION: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.

Morphine Induced Neuroprotection in Ischemic Stroke by Activating Autophagy Via mTOR-Independent Activation of the JNK1/2 Pathway.

Morphine (Mor) has exhibited efficacy in safeguarding neurons against ischemic injuries by simulating ischemic/hypoxic preconditioning (I/HPC). Concurrently, autophagy plays a pivotal role in neuronal survival during IPC against ischemic stroke. However, the involvement of autophagy in Mor-induced neuroprotection and the potential mechanisms remain elusive. Our experiments further confirmed the effect of Mor in cellular and animal models of ischemic stroke and explored its potential mechanism. The findings revealed that Mor enhanced cell viability in a dose-dependent manner by augmenting autophagy levels and autophagic flux in neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Pretreatment of Mor improved neurological outcome and reduced infarct size in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) at 1, 7 and 14 days. Moreover, the use of autophagy inhibitors nullified the protective effects of Mor, leading to reactive oxygen species (ROS) accumulation, increased loss of mitochondrial membrane potential (MMP) and neuronal apoptosis in OGD/R neurons. Results further demonstrated that Mor-induced autophagy activation was regulated by mTOR-independent activation of the c-Jun NH2- terminal kinase (JNK)1/2 Pathway, both in vitro and in vivo. Overall, these findings suggested Mor-induced neuroprotection by activating autophagy, which were regulated by JNK1/2 pathway in ischemic stroke.

Life expectancy and mental related burden of disease among people living with HIV/AIDS.

Mental health problems leads to serious disease burden among people living with HIV/AIDS (PLHIV). The study aimed at measuring the mental disorders-caused burden of disease based on PLHIV in mainland China. The data used was from the national HIV/AIDS case reporting system, life expectancy (LE) and LE-eliminated suicide were evaluated by the life-table method. The total YLLs and YLLs caused by suicide in each age group were calculated. The disability weights were estimated by the scale of depression symptoms (CES-D) from the multi-center cross-sectional survey, then calculated the corresponding YLDs as a burden of mental illness among PLHIV. Results showed that the LE had been prolonged by implementing antiviral therapy for PLHIV. The proportion of YLLs caused by suicide was the highest (5·46%) in the 15-24 age group. The YLDs in the 25-34 age group were the highest. The YLLs caused by suicide in males were higher than those in the same age group of females. The YLDs and YLLs were higher in heterosexual-infected PLHIV than in homosexual-infected PLHIV, except for YLLs in the 25-34 age group. In summary, this study first provided localized data on the disease burden caused by mental health problems among PLHIV.

Catastrophic health expenditure and health-related quality of life among older adults in Shandong, China: the moderation effect of daily care by adult children.

BACKGROUND: Catastrophic health expenditure (CHE) has a considerable impact on older people in later life, but little is known about the relationship between catastrophic health expenditure and health-related quality of life (HRQOL). The aim of this study was to examine the relationship between catastrophic health expenditure and health-related quality of life in older people, and to explore whether the daily care provided by adult children is a moderator in this relationship. METHODS: Data from the sixth National Health Services Survey in Shandong Province, China. The sample consisted of 8599 elderly people (age ≥ 60 years; 51.7% of female). Health-related quality of life was measured by the health utility value of EQ-5D-3 L. Interaction effects were analyzed using Tobit regression models and marginal effects analysis. RESULTS: The catastrophic health expenditure prevalence was 60.5% among older people in Shandong, China. catastrophic health expenditure was significantly associated with lower health-related quality of life (ß= - 0.142, P < 0.001). We found that adult children providing daily care services to their parents mitigated the effect of catastrophic health expenditure on health-related quality of life among older people (ß = 0.027, P = 0.040). CONCLUSIONS: Our findings suggested that catastrophic health expenditure was associated with health-related quality of life and the caring role of older adult children moderated this relationship. Reducing the damage caused by catastrophic health expenditure helps to improve health-related quality of life in older people. Adult children should increase intergenerational contact, provide timely financial and emotional support to reduce the negative impact of catastrophic health expenditure on health-related quality of life.

Activities of daily living limitations and the use of physical examination among older adults with informal care in China: do gender and residence make differences?

BACKGROUND: This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. METHODS: The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. RESULTS: The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P < 0.001), and there were gender and rural-urban differences. The association between ADL limitations and the use of physical examination was statistically significant in older women receiving informal care (OR = 0.65, 95% CI: 0.53, 0.80, P < 0.001). And only among urban older adults receiving informal care, those with ADL limitations had lower utilization of physical examination services than participants without ADL limitations (OR = 0.59, 95% CI: 0.47, 0.74, P < 0.001). CONCLUSIONS: Our study suggested that the relationship between ADL limitations and the use of physical examination among older adults receiving informal care differed by gender and urban-rural areas in Shandong, China. These findings implied that the government should provide more health resources and personalized physical examination service programs, especially to meet the differential needs of women and urban old adults receiving informal care, to contribute to the implementation of healthy aging strategies.

The significance of admission blood lactate and fibrinogen in pediatric traumatic brain injury: a single-center clinical study.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in pediatric patients, leading to long-term physical, cognitive, and psychological impairments. Blood lactate and fibrinogen levels have emerged as potential biomarkers associated with tissue hypoperfusion and coagulation dysfunction, respectively. However, limited research has specifically focused on the significance of these biomarkers in pediatric TBI. This study aimed to investigate the clinical significance of blood lactate and fibrinogen levels upon admission in pediatric patients with traumatic brain injury. METHODS: The medical records of 80 children with a traumatic brain injury who were admitted from January 2017 to January 2021 were retrospectively analyzed. The two groups were compared according to whether the blood lactate in the admission arterial blood gas increased and the fibrinogen content in the coagulation function decreased. The clinical data of the children in the two groups were different, and then they were divided into a good prognosis group and a poor prognosis group according to the GOS prognostic score, and the differences in the clinical indicators of the two groups were compared. RESULTS: Among the 80 patients, 33 had elevated blood lactate levels, 34 had decreased fibrinogen levels, and 29 had an unfavorable outcome (GOS < 4). Compared to the normal blood lactate group, there were no statistically significant differences in age, sex ratio, or platelet count in the elevated blood lactate group (P > 0.05). However, the elevated blood lactate group had lower Glasgow Coma Scale (GCS) scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stay, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the normal fibrinogen group, there were no statistically significant differences in age, sex ratio, or platelet count in the decreased fibrinogen group (P > 0.05). However, the decreased fibrinogen group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the favorable outcome group, there were no statistically significant differences in age, sex ratio, or platelet count in the unfavorable outcome group (P > 0.05). However, the unfavorable outcome group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, a higher incidence of pulmonary infection, a higher incidence of stress ulcers, and lower GOS scores (P < 0.05). CONCLUSION: The levels of blood lactate and fibrinogen may represent the severity of children with traumatic brain injury and may be risk factors for poor prognosis of children with traumatic brain injury.

Successful Conservative Treatment of Necrotizing Pneumonia in Pediatric Patients: Two Case Reports.

Objective: Necrotizing pneumonia is a rare and serious complication in pediatric patients, and its treatment often involves the complexity of choosing between surgical intervention and medical management. The disease is difficult to treat because of its devastating characteristics and high mortality rate, especially when considering the risks associated with surgery. The purpose of this report is to present two cases of necrotizing pneumonia in pediatric patients and demonstrate successful conservative management to provide additional insights for clinical decision-making. Case Report: We report two pediatric patients, aged 3 years 7 months and 7 years respectively, who presented with varying degrees of clinical symptoms, including persistent high fever, shortness of breath, and were confirmed to have necrotizing pneumonia after thorough diagnosis and underwent a period of intensive care. Weeks of treatment. Both patients received long-term antibiotic therapy, ventilator support, and analgesia. Conservative management including type of antibiotics, duration of treatment, specific parameters of respiratory support, and analgesic medications is detailed. Conclusion: Our case report highlights that necrotizing pneumonia can be successfully treated with conservative treatment, thus obviating the need for early surgical intervention. These findings are potentially important for guiding clinical practice, suggesting that conservative management can be an effective treatment strategy for necrotizing pneumonia in certain circumstances.

Chromatin accessibility uncovers KRAS-driven FOSL2 promoting pancreatic ductal adenocarcinoma progression through up-regulation of CCL28.

BACKGROUND: The epigenetic mechanisms involved in the progression of pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. This study aimed to identify key transcription factors (TFs) through multiomics sequencing to investigate the molecular mechanisms of TFs that play critical roles in PDAC. METHODS: To characterise the epigenetic landscape of genetically engineered mouse models (GEMMs) of PDAC with or without KRAS and/or TP53 mutations, we employed ATAC-seq, H3K27ac ChIP-seq, and RNA-seq. The effect of Fos-like antigen 2 (FOSL2) on survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis for PDAC patients. To study the potential targets of FOSL2, we performed Cleavage Under Targets and Tagmentation (CUT&Tag). To explore the functions and underlying mechanisms of FOSL2 in PDAC progression, we employed several assays, including CCK8, transwell migration and invasion, RT-qPCR, Western blotting analysis, IHC, ChIP-qPCR, dual-luciferase reporter, and xenograft models. RESULTS: Our findings indicated that epigenetic changes played a role in immunosuppressed signalling during PDAC progression. Moreover, we identified FOSL2 as a critical regulator that was up-regulated in PDAC and associated with poor prognosis in patients. FOSL2 promoted cell proliferation, migration, and invasion. Importantly, our research revealed that FOSL2 acted as a downstream target of the KRAS/MAPK pathway and recruited regulatory T (Treg) cells by transcriptionally activating C-C motif chemokine ligand 28 (CCL28). This discovery highlighted the role of an immunosuppressed regulatory axis involving KRAS/MAPK-FOSL2-CCL28-Treg cells in the development of PDAC. CONCLUSION: Our study uncovered that KRAS-driven FOSL2 promoted PDAC progression by transcriptionally activating CCL28, revealing an immunosuppressive role for FOSL2 in PDAC.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

High sensitivity and wide range flexible piezoresistive sensor based on petal-shaped MOF-derived NiCo-NPC.

Due to the advantages of high porosity, excellent conductivity, and tunable morphology, carbonized metal-organic framework (C-MOF) is expected to become an ideal material for constructing high-performance flexible pressure sensor. Herein, to achieving the suitable morphology of C-MOF for piezoresistive sensors, a rapid thermal process (RTP) was used for carbonization of NiCo-MOF, and the petal-shaped NiCo alloy nanoparticles/nanoporous carbon composites (NiCo-NPCs) were obtained. Compared with NiCo-NPCs carbonized by common thermal process (CTP), NiCo-NPCs carbonized by RTP exhibit a modified morphology with smaller particle size and larger most frequent pore diameter. Due to the modified morphology, the piezoresistive sensor with RTP-carbonized NiCo-NPCs has a high sensitivity of 62.13 kPa-1at 0-3 kPa, which is 3.46 times higher than that of the sensor with CTP-carbonized NiCo-NPCs. Meanwhile, the sensor shows an ultra-wide range of 1000 kPa, excellent cycle stability (>4000 cycles), and fast response/recovery time of 25/44 ms. Furthermore, the application of the sensor in dynamic loading test, airflow monitoring, voice recognition, and gesture detection demonstrates its great application prospects. In short, this work investigates the application of carbonized NiCo-MOFs in flexible pressure sensors, and provides a new strategy to improve the performance of piezoresistive sensors with porous carbon derived from MOFs.

Ultra-sensitive specific detection of nucleic acids in pathogenic infections by Ta2C-MXene sensitization-based ultrafine plasmon spectroscopy combs.

Accurate and rapid population-scale screening techniques based on SARS-CoV-2 RNA are essential in preventing and controlling the COVID-19 epidemic. However, the sensitivity and specificity of the assay signal are challenged by the problems of target dilution and sample contamination inherent in high-volume pooled testing. Here, we reported a collaborative system of high-loaded hybrid probes targeting N and OFR1a coupling with the novel Ta2C-M/Au/TFBG biosensor, providing high-intensity vector signals for detecting SARS-CoV-2. The method relies on a segmental modification approach to saturable modify multiple activation sites of SARS-CoV-2 on the high-performance Ta2C-M surface. The coupling of multi-site synergy with composite excited TFBG results in excellent signal transduction, detection limits (0.2 pg/mL), and hybridization efficiency. Without relying on amplification, the collaborative system achieved specific differentiation of 30 clinical samples in an average diagnostic time of 1.8 min. In addition, for the first time, a kinetic determination of dilution mixed samples was achieved and showed a high-intensity carrier signal and fantastic stability. Therefore, it can be used as a collaborative, integrated tool to play a massive role in the screening, prevention, and control of COVID-19 and other epidemics.

Prenatal diagnosis of total anomalous pulmonary venous connection using 2D and HDlive flow combined with spatiotemporal image correlation.

OBJECTIVES: The objective of this study is to examine the application value of two-dimensional (2D) and high-definition live (HDlive) flow combined with spatiotemporal image correlation (STIC) in diagnosing fetal total anomalous pulmonary venous connection (TAPVC). METHODS: Seventeen cases of fetal TAPVC were diagnosed using 2D and HDlive Flow combined with STIC. These cases were then retrospectively analyzed to examine the value of using 2D and HDlive Flow combined with STIC in the diagnosis of TAPVC. RESULTS: 2D and HDlive Flow combined with STIC detected 13 cases of supracardiac TAPVC (two isolated cases, seven cases with right atrial isomerism (RAI), four cases with other complex malformations), one case of isolated intra-cardiac TAPVC, and three cases of cardiac TAPVC (two isolated cases and one case with complex congenital heart anomaly). Small left atrium (LA), the absence of PVs drainage into the LA and the increased retroatrial distance between LA and the descending aorta (DAo) were significant signs that should raise the suspicion of fetal TAPVC. HDlive Flow combined with STIC can dynamically display the TAPVC which may assit the prenatal diagnosis of TAPVC. CONCLUSION: 2D and HDlive Flow combined with STIC can assit the diagnosis of fetal TAPVC abnormalities and has important clinical value.

Enhancing the Performance of Evolutionary Algorithm by Differential Evolution for Optimizing Distillation Sequence.

Optimal synthesis of distillation sequence is a complex problem in chemical processes engineering, which involves process structure optimization and operation parameters optimization. The study of the synthesis of distillation sequence is a crucial step toward improving the efficiency of chemical processes and reducing greenhouse gas emissions. This work introduced the concept of binary tree to encode the distillation sequence. The performance of the six evolutionary algorithms was evaluated by solving a 14-component distillation sequence synthesis problem. The best algorithm was used to optimize the operation parameters of a triple-column distillation process. The total annual cost and CO2 emissions were considered as the metrics to evaluate the performance of triple-column distillation processes. As a result, NSGA-II-DE was found to be the best one of the six tested evolutionary algorithms. Then, NSGA-II-DE was applied to the distillation sequence optimization to find the best operating parameters, which led to a significant reduction in CO2 emission and total annual costs.

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer.

Fusobacterium nucleatum (F. nucleatum), which has been associated with colorectal carcinogenesis, can impair anti-tumour immunity, and actively invade colon epithelial cells. Considering the critical role of autophagy in host defence against microorganisms, we hypothesised that autophagic activity of tumour cells might influence the amount of F. nucleatum in colorectal cancer tissue. Using 724 rectal and colon cancer cases within the Nurses' Health Study and the Health Professionals Follow-up Study, we evaluated autophagic activity of tumour cells by immunohistochemical analyses of BECN1 (beclin 1), MAP1LC3 (LC3), and SQSTM1 (p62) expression. We measured the amount of F. nucleatum DNA in tumour tissue by quantitative polymerase chain reaction (PCR). We conducted multivariable ordinal logistic regression analyses to examine the association of tumour BECN1, MAP1LC3, and SQSTM1 expression with the amount of F. nucleatum, adjusting for potential confounders, including microsatellite instability status; CpG island methylator phenotype; long-interspersed nucleotide element-1 methylation; and KRAS, BRAF, and PIK3CA mutations. Compared with BECN1-low cases, BECN1-intermediate and BECN1-high cases were associated with lower amounts of F. nucleatum with odds ratios (for a unit increase in three ordinal categories of the amount of F. nucleatum) of 0.54 (95% confidence interval, 0.29-0.99) and 0.31 (95% confidence interval, 0.16-0.60), respectively (Ptrend < 0.001 across ordinal BECN1 categories). Tumour MAP1LC3 and SQSTM1 levels were not significantly associated with the amount of F. nucleatum (Ptrend > 0.06). Tumour BECN1, MAP1LC3, and SQSTM1 levels were not significantly associated with patient survival (Ptrend > 0.10). In conclusion, tumour BECN1 expression is inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting a possible role of autophagy in the elimination of invasive microorganisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Long non-coding RNA ADAMTS9-AS1 suppresses colorectal cancer by inhibiting the Wnt/ß-catenin signalling pathway and is a potential diagnostic biomarker.

Long non-coding RNAs (lncRNAs) have come out as critical molecular regulators of human tumorigenesis. In this study, we sought to identify and functionally characterize lncRNAs as potential mediators of colorectal cancer progression. We screened and identified a novel lncRNA, ADAMTS9-AS1, which was significantly decreased in colorectal cancer tissues and was correlated with clinical outcome of patients according to The Cancer Genome Atlas (TCGA) database. In addition, ADAMTS9-AS1 regulated cell proliferation and migration both in vitro and in vivo. Bioinformatics analysis revealed that overexpression of lncRNA-ADAMTS9-AS1 preferentially affected genes that were linked to proliferation and migration. Mechanistically, we found that ADAMTS9-AS1 obviously suppressed ß-catenin, suggesting that Wnt signalling pathway participates in ADAMTS9-AS1-mediated gene transcriptional regulation in the suppression of colorectal tumorigenesis. Finally, we found that exosomal ADAMTS9-AS1 could serve as a diagnostic biomarker for colorectal cancer with AUC = 0.835 and 95% confidence interval = 0.777-0.911. Our data demonstrated that ADAMTS9-AS1 might play important roles in colorectal cancer by suppressing oncogenesis. Targeting ADAMTS9-AS1 may have potential clinical applications in colorectal cancer prognosis and treatment as an ideal therapeutic target. Finally, exosomal lncRNA-ADAMTS9-AS1 is a promising, novel diagnostic biomarker for colorectal cancer.

Correction to: Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer.

An amendment to this paper has been published and can be accessed via the original article.

An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer.

BACKGROUND: Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies. METHODS: We examined Crohn's-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load. RESULTS: Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42-0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12-0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2). CONCLUSIONS: The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.