Cytoplasmic HYL1 modulates miRNA-mediated translational repression.

MicroRNAs (miRNAs) control various biological processes by repressing target mRNAs. In plants, miRNAs mediate target gene repression via both mRNA cleavage and translational repression. However, the mechanism underlying this translational repression is poorly understood. Here, we found that Arabidopsis thaliana HYPONASTIC LEAVES1 (HYL1), a core component of the miRNA processing machinery, regulates miRNA-mediated mRNA translation but not miRNA biogenesis when it localized in the cytoplasm. Cytoplasmic HYL1 localizes to the endoplasmic reticulum and associates with ARGONAUTE1 (AGO1) and ALTERED MERISTEM PROGRAM1. In the cytoplasm, HYL1 monitors the distribution of AGO1 onto polysomes, binds to the mRNAs of target genes, represses their translation, and partially rescues the phenotype of the hyl1 null mutant. This study uncovered another function of HYL1 and provides insight into the mechanism of plant gene regulation.

KIFC3 regulates progression of hepatocellular carcinoma via EMT and the AKT/mTOR pathway.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. Despite an overall downward trend in cancer mortality, HCC-related mortality continues to increase. KIFC3 is involved in cell division and cancers. However, the role of KIFC3 in HCC has yet to be elucidated. METHODS: A total of 36 cases of HCC tissues, 4 HCC cell lines, and TCGA databases were searched to explore the expression of KIFC3 in HCC. Subsequently, Western blot analysis, immunofluorescence, bioinformatic analysis, molecular docking, and Co-IP were performed to investigate the molecular mechanisms of KIFC3 in HCC. RESULT: We found that the expression of KIFC3 was upregulated in HCC, and high KIFC3 expression was related to poor overall survival. In addition, the knockdown of KIFC3 inhibited the proliferation, migration, and invasion of HCC cells in vitro, and impeded the growth of HCC in vivo, while overexpression of KIFC3 in HCC cells revealed the opposite effect. Mechanistically, KIFC3 promotes the progression of HCC through the PI3K/AKT/mTOR signalling. And KIFC3 had slight effect on the protein expression of p-PI3K, p-AKT and p-mTOR in TRIP13-ablated or LY294002-treated HCC cells. The KIFC3 knockdown could further enhance the inhibitory effect of LY294002. CONCLUSION: Our data revealed that KIFC3 is upregulated in HCC and may serve as a novel biomarker for predicting survival in HCC patients. Targeting KIFC3 may serve as a novel therapeutic strategy for HCC patients.

Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aß-induced neurotoxicity.

BACKGROUND: Neuroinflammation plays a critical role in Amyloid-ß (Aß) pathophysiology. The cytokine, interleukin-17A (IL-17) is involved in the learning and memory process in the central nervous system and its level was reported to be increased in Alzheimer's disease (AD) brain, while the effect of IL-17 on the course of Aß has not been well defined. METHODS: Here, we used APP/PS1 mice to detect the IL-17 expression level. Primary hippocampal neurons were treated with IL-17, and immunofluorescence was used to investigate whether IL-17 induced neuron damage. At the same time, male C57BL/6 mice were injected with Aß42 to mimic the Aß model. Then IL-17 neutralizing antibody (IL-17Ab) was used to inject into the lateral ventricle, and the Open field test, Novel Objective Recognition test, Fear condition test were used to detect cognitive function. LTP was used to assess synaptic plasticity, molecular biology technology was used to assess the IL-17/TRAF6/NF-κB pathway, and ELISA was used to detect inflammatory factors. RESULTS: Altogether, we here found that IL-17 was increased in APP/PS1 mice, and it induced neural damage by the administration to primary hippocampal neurons. Interestingly, Using Aß42 mice, the results showed that the level of IL-17 was increased in Aß42 model mice, and IL-17Ab could ameliorate Aß-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation the TRAF6/NF-κB pathway. CONCLUSION: These findings highlight the pathogenic role of IL-17 in Aß induced-synaptic dysfunction and cognitive deficits. Inhibition of IL-17 could ameliorate Aß-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation of the TRAF6/NF-κB pathway, which provides new clues for the mechanism of Aß-induced cognitive impairments, and a basis for therapeutic intervention.

Dihydrokaempferol attenuates CCl4-induced hepatic fibrosis by inhibiting PARP-1 to affect multiple downstream pathways and cytokines.

The pathophysiological mechanism of hepatic fibrosis (HF) is related to the excessive activation of the DNA repair enzyme poly ADP-ribose polymerase-1 (PARP-1). The drugs, targeting PARP-1, are scarce. Therefore, the lead compound, moderately inhibiting PARP-1, with anti-HF properties should be identified. This study screened dihydrokaempferol (DHK) from herbs based on preliminary studies to intervene in a CCl4-induced liver injury and HF model in mice. In vitro, the expression levels of PARP-1-regulated related proteins and phosphorylation were examined. The binding pattern of DHK and PARP-1 was analyzed using molecular docking and molecular dynamics platforms. The results showed that DHK could significantly attenuate CCl4-induced liver injury and HF in mice. Moreover, it could also attenuate the toxic effects of CCl4 on HepG2 and inhibit α-SMA and Collagen 1/3 synthesis of LX-2 cells in-vitro. Molecular docking revealed that DHK could competitively bind to the Glu-988 and His-862 residues of the upstream DNA repair enzyme PARP-1, moderately inhibiting its overactivation. This led to maintaining NAD+ levels and energy metabolism in hepatocytes and inhibiting the activation of PARP-1-regulated downstream signaling pathways (TGF-ß1, etc.), related proteins (p-Smd2/3, etc.), and inflammatory mediators while acting indirectly. Thus, DHK could attenuate CCl4-induced liver injury and HF in mice in a different mechanism from those of the existing reported flavonoids. It was associated with inhibiting the expression of downstream pathways and related cytokines by competitively binding to PARP-1. This study might provide a basis and direction for the design and exploration of anti-HF lead compounds.

Construction and validation of a nomogram of risk factors and cancer-specific survival prognosis for combined lymphatic metastases in patients with early-onset colorectal cancer.

PURPOSE: This study aimed to investigate the risk and prognostic factors of lymph node metastasis (LNM) in early-onset colorectal cancer (EO-CRC) and to develop nomograms for quantitatively predicting LNM and the cancer-specific survival (CSS). METHODS: A total of 22,405 EO-CRC patients were included in this study using the SEER database from 2010 to 2017. Logistic and Cox regression were used to identify risk and the potential prognostic factors, respectively, for EO-CRC with LNM. Subsequently, nomograms regarding the risk of LNM in EO-CRC patients and its corresponding CSS were constructed based on these factors. The discriminative ability, calibration and clinical usefulness of the nomograms were assessed by the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA). RESULTS: T-stage and pathological grade were the most represented factors in the predicted LNM nomogram, while histological type and combined distant metastases were the most represented in the nomogram for CSS in EO-CRC patients with LNM (all P < 0.05). The nomogram constructed based on the prognostic factors screened by Cox regression had good performance with C-index of 0.807 and 0.802 for the training and validation cohorts, respectively. The calibration curve showed that the nomograms' predictions were in line with actual observations. Additionally, the ROC curves indicated good discrimination, and the DCA curves implied significant clinical utility of the nomograms. CONCLUSION: The nomograms we constructed have significant performance in predicting the incidence and prognosis of LNM in EO-CRC patients, which may help clinicians to make better treatment decision making.

Association between diet soft drink consumption and metabolic dysfunction-associated steatotic liver disease: findings from the NHANES.

BACKGROUND: Lifestyle change plays a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). In recent years, diet soft drinks that emphasize "zero sugar and zero calories" have become all the rage, but whether diet soft drink consumption is associated with MASLD is not clear. METHODS: This study included data from the National Health and Nutrition Examination Surveys (NHANES) in 2003-2006. The assessment of MASLD status primarily relied on the Fatty Liver Index (FLI). Weighted multiple Logistic regression models were constructed to evaluate the association between diet soft drink consumption and MASLD. Additionally, mediation analysis was performed to examine the mediating effect of body mass index (BMI). RESULTS: A total of 2,378 participants were included in the study, among which 1,089 individuals had MASLD, and the weighted prevalence rate was 43.64%. After adjusting for variables related to demographic, lifestyle, and metabolic syndrome, excessive diet soft drink consumption (the "always" frequency) remained significantly associated with the occurrence of MASLD (OR = 1.98, 95%CI = 1.36-2.89, P = 0.003). It was estimated that 84.7% of the total association between diet soft drink consumption and MASLD was mediated by BMI (P < 0.001). CONCLUSIONS: Excessive diet soft drink consumption was associated with the occurrence of MASLD. BMI may play a mediating role in the association between diet soft drink consumption and MASLD.

Thymoquinone induces apoptosis and protective autophagy in gastric cancer cells by inhibiting the PI3K/Akt/mTOR pathway.

Gastric cancer (GC) is often diagnosed in the advanced stages with a poor prognosis. Thymoquinone (TQ) is known for its antitumor activity; however, the specific mechanism in GC remains unknown. In our study, TQ inhibited GC cell proliferation and induced apoptosis and autophagy in a concentration-dependent manner. Transmission electron microscopy showed increased autophagosome formation in GC cells treated with TQ. Meanwhile, the LC3B puncta and LC3BII protein levels were significantly increased in GC cells, while p62 expression was significantly decreased. The autophagy inhibitor, Bafilomycin A1 enhanced TQ-inhibited proliferation and TQ-induced apoptosis, suggesting that TQ-induced autophagy has a protective effect on GC cells. Furthermore, TQ decreased the phosphorylation levels of phosphatidylinositol-4,5-bisphosphate 3 kinase (PI3K), protein kinase B (Akt), and mechanistic target of rapamycin (mTOR). The PI3K agonist partially rescued TQ-induced autophagy and apoptosis. Finally, in vivo experiments showed that TQ could inhibit tumor growth and promote apoptosis and autophagy. This study provides new insights into the specific mechanism for the anti-GC effect of TQ. TQ inhibits the proliferation of GC cells and induces apoptosis and protective autophagy by inhibiting the PI3K/Akt/mTOR pathway. The results suggest that the combination of TQ and autophagy inhibitors might be a potential chemotherapeutic strategy for GC.

Bibliometric analysis of N6-methyladenosine in cancer: landscapes, highlights and trending topics.

Background: N6-methyladenosine (m6A) is crucial in cancer and is being intensively studied. Aim: This bibliometric analysis seeks a broad picture of the role of m6A in cancer to guide and broaden future research. Methods: Publications were retrieved from Web of Science Core Collection and PubMed from 2000 to 2021, with keywords 'm6A' and 'cancer', and analyzed in biblioshiny and VOSviewer. Results: A total of 1013 documents were included, and China and the USA were the top countries with close collaboration. Mechanisms and predictive biomarkers of m6A regulator genes were highlighted. Cross-integration of m6A and other research hot spots, including 'immunotherapy', 'hypoxia' and 'polymorphism', were frontiers of m6A in cancer. Conclusion: This bibliometric study offered an updated perspective on m6A in cancer.

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.

MicroRNA319a regulates plant resistance to Sclerotinia stem rot.

MicroRNA319a (miR319a) controls cell division arrest in plant leaves by inhibiting the expression of TCP (TEOSINTE BRANCHED 1/CYCLOIDEA/PCF) family genes. However, it is unclear whether miR319a influences infection by necrotrophic pathogens and host susceptibility. In this study, we revealed that miR319a affects plant resistance to stem rot disease caused by Sclerotinia sclerotiorum. In Brassica rapa plants infected with S. sclerotiorum, miR319a levels increased while the expression levels of several BraTCP genes significantly decreased compared with those of uninfected plants. Overexpression of BraMIR319a in B. rapa increased the susceptibility of the plants to S. sclerotiorum and aggravated stem rot disease, whereas overexpression of BraTCP4-1 promoted plant resistance. RNA sequencing data revealed a potential relationship between miR319a and pathogen-related WRKY genes. Chromatin immunoprecipitation, electrophoretic mobility shift, and reporter transaction assays showed that BraTCP4-1 could bind to the promoters of WRKY75, WRKY70, and WRKY33 and directly activate these pathogen-related genes. Moreover, the expression levels of WRKY75, WRKY70, and WRKY33 in plants overexpressing BraMIR319a decreased significantly, whereas those of plants overexpressing BraTCP4-1 increased significantly, relative to the wild type. These results suggest that miR319a and its target gene BraTCP4 control stem rot resistance through pathways of WRKY genes.

Fusobacterium nucleatum facilitates ulcerative colitis through activating IL-17F signaling to NF-κB via the upregulation of CARD3 expression.

Accumulating evidence links Fusobacterium nucleatum with ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal inflammation in UC remains poorly defined. Here, we first examined the abundance and impact of F. nucleatum on disease activity in UC tissues. Next, we isolated a strain of F. nucleatum from UC tissues and explored whether F. nucleatum aggravates the intestinal inflammatory response in vitro and in vivo. We also examined whether F. nucleatum infection involves the NF-κB or IL-17F signaling pathways. Our data showed that F. nucleatum was enriched in 51.78% of UC tissues and was correlated with the clinical course, clinical activity and refractory behavior of UC (p < 0.05). Furthermore, we demonstrated that F. nucleatum promoted intestinal epithelial damage and the expression of the inflammatory cytokines IL-1ß, Il-6, IL-17F and TNF-α. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) through NOD2 to activate the IL-17F/NF-κB pathway in vivo and in vitro. Thus, F. nucleatum orchestrates a molecular network involving CARD3 and IL-17F to control the UC process. Measuring and targeting F. nucleatum and its associated pathways will yield valuable insight into the prevention and treatment of UC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Clinical characteristics of COVID-19 complicated with pleural effusion.

BACKGROUND: Epidemiological and clinical features of patients with corona virus disease 2019 (COVID-19) were well delineated. However, no researches described the patients complicated with pleural effusion (PE). In the present study, we aimed to clinically characterize the COVID-19 patients complicated with PE and to create a predictive model on the basis of PE and other clinical features to identify COVID-19 patients who may progress to critical condition. METHODS: This retrospective study examined 476 COVID-19 inpatients, involving 153 patients with PE and 323 without PE. The data on patients' past history, clinical features, physical checkup findings, laboratory results and chest computed tomography (CT) findings were collected and analyzed. LASSO regression analysis was employed to identify risk factors associated with the severity of COVID-19. RESULTS: Laboratory findings showed that patients with PE had higher levels of white blood cells, neutrophils, lactic dehydrogenase, C-reactive protein and D-dimer, and lower levels of lymphocytes, platelets, hemoglobin, partial pressure of oxygen and oxygen saturation. Meanwhile, patients with PE had higher incidence of severe or critical illness and mortality rate, and longer hospital stay time compared to their counterparts without pleural effusion. Moreover, LASSO regression analysis exhibited that pleural effusion, lactic dehydrogenase (LDH), D-dimer and total bilirubin (TBIL) might be risk factors for critical COVID-19. CONCLUSIONS: Pleural effusion could serve as an indicator for severe inflammation and poor clinical outcomes, and might be a complementary risk factor for critical type of COVID-19.

Gastrointestinal Symptoms Onset in COVID-19 Patients in Wuhan, China.

BACKGROUND: Early detection is critical in limiting the spread of 2019 novel coronavirus (COVID-19). Although previous data revealed characteristics of GI symptoms in COVID-19, for patients with only GI symptoms onset, their diagnostic process and potential transmission risk are still unclear. METHODS: We retrospectively reviewed 205 COVID-19 cases from January 16 to March 30, 2020, in Renmin Hospital of Wuhan University. All patients were confirmed by virus nuclei acid tests. The clinical features and laboratory and chest tomographic (CT) data were recorded and analyzed. RESULTS: A total of 171 patients with classic symptoms (group A) and 34 patients with only GI symptoms (group B) were included. In patients with classical COVID-19 symptoms, GI symptoms occurred more frequently in severe cases compared to non-severe cases (20/43 vs. 91/128, respectively, p < 0.05). In group B, 91.2% (31/34) patients were non-severe, while 73.5% (25/34) patients had obvious infiltrates in their first CT scans. Compared to group A, group B patients had a prolonged time to clinic services (5.0 days vs. 2.6 days, p < 0.01) and a longer time to a positive viral swab normalized to the time of admission (6.9 days vs. 3.3 days, respectively, p < 0.01). Two patients in group B had family clusters of SARS-CoV-2 infection. CONCLUSION: Patients with only GI symptoms of COVID-19 may take a longer time to present to healthcare services and receive a confirmed diagnosis. In areas where infection is rampant, physicians must remain vigilant of patients presenting with acute gastrointestinal symptoms and should do appropriate personal protective equipment.

Development and validation a simple model for identify malignant ascites.

The differential diagnosis of benign ascites and malignant ascites is incredibly challenging for clinicians. This research aimed to develop a user-friendly predictive model to discriminate malignant ascites from non-malignant ascites through easy-to-obtain clinical parameters. All patients with new-onset ascites fluid were recruited from January 2014 to December 2018. The medical records of 317 patients with ascites for various reasons in Renmin Hospital of Wuhan University were collected and reviewed retrospectively. Thirty-six parameters were included and selected using univariate logistic regression, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses to establish a mathematical model for differential diagnosis, and its diagnostic performance was validated in the other groups. Age, cholesterol, hypersensitivity C-reactive protein (hs-CRP) in serum, ascitic fluid adenosine deaminase (AF ADA), ascitic fluid lactate dehydrogenase (AF LDH) involvement in a 5-marker model. With a cut-off level of 0.83, the sensitivity, specificity, accuracy, and area under the ROC of the model for identifying malignant ascites in the development dataset were 84.7%, 88.8%, 87.6%, and 0.874 (95% confidence interval [CI], 0.822-0.926), respectively, and 80.9%, 82.6%, 81.5%, and 0.863 (95% CI,0.817-0.913) in the validation dataset, respectively. The diagnostic model has a similar high diagnostic performance in both the development and validation datasets. The mathematical diagnostic model based on the five markers is a user-friendly method to differentiate malignant ascites from benign ascites with high efficiency.

Changes in levels of coagulation parameters in different trimesters among Chinese pregnant women.

BACKGROUND: This article is to explore changes in levels of coagulation parameters in different trimesters among healthy pregnant women in China. METHODS: A total of 760 eligible women were enrolled (first-trimester group: n = 183, second-trimester group: n = 183, third-trimester group: n = 263, non-pregnant group: n = 131). Seven parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrinogen degradation products (FDP), and antithrombin III (ATIII), of all participants were collected. The non-parametric 2.5th-97.5th percentiles reference intervals were calculated for each parameter. RESULTS: The reference intervals for FIB, PT, APTT, TT, FDP, DD, and ATIII at first trimester were 2.11-4.32 g/L, 10.90-13.85 s, 24.60-39.28 s, 12.95-15.88 s, 0.04-2.55 µg/mL, 0.03-1.15 µg/mL, and 75.57%-125.31%, respectively. The reference intervals at second trimester were 2.31-4.77 g/L, 9.70-12.64 s, 24.16-35.43 s, 12.95-15.88 s, 0.15-7.40 µg/mL, 0.08-2.13 µg/mL, and 74.35%-119.28%, respectively. For the third-trimester, the intervals were 2.39-4.96 g/L, 9.20-11.95 s, 23.90-35.51 s, 13.41-18.00 s, 0.55-13.43 µg/mL, 0.15-3.60 µg/mL, and 71.61%-118.29%, respectively. The third-trimester group showed decreased PT, APTT, and ATIII and increased FIB, TT, DD and FDP as compared with the other groups. CONCLUSION: In this study, level changes of coagulation parameters in different trimesters were observed. And the ranges for coagulation parameters were presented, which may provide some reference for clinicians to more accurately monitor the coagulation and fibrinolytic system in pregnant women.

Factors influencing risk perception and nosocomial infection prevention practices of frontline nurses during the COVID-19 pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, exploring factors influencing nosocomial infection among frontline nurses may provide evidence to optimize prevention strategies in hospitals. METHOD: A large-scale online questionnaire survey of nurses' state-trait anxiety, job burnout, risk perception, workplace safety perception, knowledge about nosocomial infection, and preventive practices was conducted with 2795 frontline nurses working in the COVID-19 wards of six hospitals in Hubei Province, China, from February 1 to April 1, 2020. The questionnaire data were analyzed using the structural equation modeling (SEM) method to reveal the mechanisms influencing nurses' risk perception and preventive practices related to nosocomial COVID-19 infection. RESULTS: A model of the factors that influence nurses' risk perception and preventive practices regarding nosocomial COVID-19 infection was established. The model verified hypotheses regarding the impact of nurses' risk perception and preventive practices. Notably, the hypothesis that risk perception has an impact on nurses' preventive practices regarding nosocomial infection is not valid. Moreover, different marital and educational conditions are associated with significant differences in the impact of state anxiety on the execution of preventive practices, the impact of workplace safety perceptions on risk perception, and the impact of workplace safety perceptions on the execution of preventive practices. The effect of state anxiety on preventive practices differed significantly with different durations of work experience. CONCLUSIONS: According to the results of the influencing factor model, promoting the quality of training on nosocomial infection, meliorating workplace safety, and conducting timely and effective psychological interventions would aid in improving nurses' preventive practices. Meliorating workplace safety and easing state anxiety would be beneficial to reduce nurses' risk perception. These strategies are conducive to the optimization of policies for preventing nosocomial COVID-19 infections and similar infectious diseases.

Mining TCGA database for genes of prognostic value in gastric cancer microenvironment.

Gastric cancer (GC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Emerging evidence suggests that tumour microenvironment cells play a vital role in the development and prognosis of GC. To investigate the possible effect of stromal scores and immune scores on the overall survival (OS) on the GC patients, we divided GC patients into 'high' and 'low' groups based on their stromal and immune scores, and found differentially expressed genes related to prognosis of GC patients. Functional enrichment analysis and GSVA further revealed that focal adhesion and ECM-receptor interaction are associated with GC patients' survival. Finally, we analysed the effects of genes commonly involved in focal adhesion and ECM-receptor interaction on GC patients' survival and validated our results in another GC cohort from GEO data sets. In conclusion, we obtained a list of tumour microenvironment-related genes that predict poor prognosis in GC patients.

Flexible Three-Dimensional Net for Intravascular Fishing of Circulating Tumor Cells.

Current strategies for in vitro isolation of circulating tumor cells (CTCs) fail to detect extremely rare CTCs heterogeneously distributed in blood. It is possible to devise methods for in vivo capture of CTCs based on processing almost all of the blood in the human body to improve detection sensitivity, but the complicated manipulation, biosafety concerns, and limited capture efficiency of conventional detection strategies prohibit their implementation in the clinic. Herein, we present a flexible three-dimensional (3-D) CTC-Net probe for intravascular collection of CTCs. The CTC-Net, consisting of a 3-D elastic scaffold with an interconnected, spatially distributed network accommodates a large quantity of immobilized antibodies and provides an enhanced substrate-cell contact frequency, which results in an enhanced capture efficiency and effective detection of heterogeneous CTCs. The as-prepared CTC-Net can be readily compressed and injected into blood vessels and fully unfolded to form a 3-D "fishing-net" structure for capture of the CTCs, and then retracted for imaging and downstream gene analysis of the captured CTCs. Significant advantages for the CTC-Net over currently available in vitro and in vivo procedures are demonstrated for detection of extremely rare CTCs from wild-type rats and successful capture of CTCs and CTC clusters before metastasis in the case of tumor-bearing rats. Our research demonstrates for the first time the use of a 3-D scaffold CTC-Net probe for in vivo capture of CTCs. The method shows exceptional performance for cell capture, which is readily implemented and holds great potential in the clinic for early diagnosis of cancer.

Glandular orientation and shape determined by computational pathology could identify aggressive tumor for early colon carcinoma: a triple-center study.

BACKGROUND: Identifying the early-stage colon adenocarcinoma (ECA) patients who have lower risk cancer vs. the higher risk cancer could improve disease prognosis. Our study aimed to explore whether the glandular morphological features determined by computational pathology could identify high risk cancer in ECA via H&E images digitally. METHODS: 532 ECA patients retrospectively from 2 independent data centers, as well as 113 from The Cancer Genome Atlas (TCGA), were enrolled in this study. Four tissue microarrays (TMAs) were constructed across ECA hematoxylin and eosin (H&E) stained slides. 797 quantitative glandular morphometric features were extracted and 5 most prognostic features were identified using minimum redundancy maximum relevance to construct an image classifier. The image classifier was evaluated on D2/D3 = 223, D4 = 46, D5 = 113. The expression of Ki67 and serum CEA levels were scored on D3, aiming to explore the correlations between image classifier and immunohistochemistry data and serum CEA levels. The roles of clinicopathological data and ECAHBC were evaluated by univariate and multivariate analyses for prognostic value. RESULTS: The image classifier could predict ECA recurrence (accuracy of 88.1%). ECA histomorphometric-based image classifier (ECAHBC) was an independent prognostic factor for poorer disease-specific survival [DSS, (HR = 9.65, 95% CI 2.15-43.12, P = 0.003)]. Significant correlations were observed between ECAHBC-positive patients and positivity of Ki67 labeling index (Ki67Li) and serum CEA. CONCLUSION: Glandular orientation and shape could predict the high risk cancer in ECA and contribute to precision oncology. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.

Exosomes derived from T regulatory cells relieve inflammatory bowel disease by transferring miR-195a-3p.

Previous studies have demonstrated the therapeutic effects of regulatory T (Treg) cells on inflammatory bowel disease (IBD), but the mechanism is not well-understood. Exosomes have been proposed as a novel mechanism underlying the action of Tregs. This study aimed to investigate the therapeutic effects of exosomes secreted by Treg cells (Treg-Exo) on IBD and to explore the underlying mechanism. Treg-Exo was isolated from BALB/c mouse spleen mononuclear cells and then injected into a murine model of IBD induced by dextran sodium sulfate (DSS) exposure. A co-culture model of Treg-Exo and colonic epithelial YAMC cells in the presence of TNF-α was used to investigate the communication between Tregs and intestinal epithelial cells. in vitro results showed that Treg-Exo could be transferred to YAMC cells where Treg-Exo promoted cell proliferation and inhibited cell apoptosis. Animal experiments showed that Treg-Exo administration alleviated the DSS-induced IBD in mice. The therapeutic effects of Treg-Exo both in vitro and in vivo were eliminated when miR-195a-3p expression was inhibited in Treg-Exo. The pro-apoptotic Caspase 12 was identified as a direct target of miR-195a-3p. In conclusion, Treg-Exo alleviated the DSS-induced IBD through transferring miR-195a-3p.