Sleep quality during pregnancy and fetal growth: A prospective cohort study.

The aim of this study is to investigate the association between sleep quality during pregnancy and fetal growth. Pregnant women and their fetuses at 16-20 gestational weeks in Nantong Maternal and Child Health Hospital were recruited. Women were classified as having "good sleep quality" (Pittsburgh Sleep Quality Index score ≤ 5) and "poor sleep quality" (Pittsburgh Sleep Quality Index score > 5) according to the Pittsburgh Sleep Quality Index scores. The fetal growth was evaluated by three ultrasonographic examinations, birth weight and birth length. We used general linear model and multiple linear regression models to estimate the associations. A total of 386 pairs of mother and infant were included in the data analysis. After adjusting for gestational weight gain, anxiety and depression, fetuses in the good sleep quality group had greater abdominal circumference (p = 0.039 for 28-31+6 weeks gestation, p = 0.012 for 37-40+6 weeks gestation) and femur length (p = 0.014 for 28-31+6 weeks gestation, p = 0.041for 37-40+6 weeks gestation) at 28-31+6 weeks gestation and 37-40+6 weeks gestation, and increased femur length (p = 0.007) at 28-31+6 weeks gestation. Birth weights (p = 0.018) were positively associated with sleep quality. Poor sleep quality was associated with poor intrauterine physical development, decreased abdominal circumference and femur length, and lower birth weight after adjusting for confounding factors. Attention to the fetal growth of pregnant women with poor sleep quality has the potential to decrease the risk of adverse fetal outcomes.

B63: The Most Stable Bilayer Structure with Dual Aromaticity.

The emergence of a bilayer B48 cluster, which has been both theoretically predicted and experimentally observed, as well as the recent experimental synthesis of bilayer borophene sheets on Ag and Cu surfaces, has generated tremendous curiosity in the bilayer structures of boron clusters. However, the connection between bilayer boron cluster and bilayer borophene remains unknown. By combining a genetic algorithm and density functional theory calculations, a global search for the low-energy structures of the B63 cluster was conducted, revealing that the Cs bilayer structure with three interlayer B-B bonds is the most stable bilayer structure. This structure was further examined in terms of its structural stability, chemical bonding, and aromaticity. Interestingly, the interlayer bonds induce strong electronegativity and robust aromaticity. Furthermore, the dual aromaticity stems from diatropic currents originating from virtual translational transitions for both σ and π electrons. This unprecedent bilayer boron cluster is anticipated to enrich the concept of dual aromaticity and serve as a potential precursor for bilayer borophene.

Mixed probiotics reduce the severity of stress-induced depressive-like behaviors.

In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.

GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.

BACKGROUND: Research has indicated that long-term sleep deprivation can lead to immune dysfunction and participate in the occurance and progression of tumors. However, the relationship between sleep deprivation and colon cancer remains unclear. This study explored the specific mechanism through which sleep deprivation promotes the proliferation and migration of colon cancer, with a focus on the neurotransmitter GABA. METHODS: Chronic sleep deprivation mice model were used to investigate the effect of sleep disorder on tumors. We detected neurotransmitter levels in the peripheral blood of mice using ELISA. CCK-8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the effect of GABA on colon cancer cells, while immunofluorescence showed the distribution of macrophages in lung metastatic tissues. We isolated exosomes from a GABA-induced culture medium to explore the effects of GABA-induced colon cancer cells on macrophages. Gain- and loss-of-function experiments, luciferase report analysis, immunohistochemistry, and cytokine detection were performed to reveal the crosstalk between colon cancer cells and macrophages. RESULTS: Sleep deprivation promote peripheral blood GABA level and colon cancer cell proliferation and migration. Immunofluorescence analysis revealed that GABA-induced colon cancer metastasis is associated with enhanced recruitment of macrophages in the lungs. The co-culture results showed that GABA intensified M2 polarization of macrophage induced by colon cancer cells. This effect is due to the activation of the macrophage MAPK pathway by tumor-derived exosomal miR-223-3p. Furthermore, M2-like macrophages promote tumor proliferation and migration by secreting IL-17. We also identified an endogenous miR-223-3p downregulation of the E3 ligase CBLB, which enhances the stability of cMYC protein and augments colon cancer cells proliferation and migration ability. Notably, cMYC acts as a transcription factor and can also regulate the expression of miR-223-3p. CONCLUSION: Our results suggest that sleep deprivation can promote the expression of miR-223-3p in colon cancer cells through GABA, leading to downregulation of the E3 ligase CBLB and inhibition of cMYC ubiquitination. Simultaneously, extracellular miR-223-3p promotes M2-like macrophage polarization, which leads to the secretion of IL-17, further enhancing the proliferation and migration of colon cancer cells.

Machine learning methods for accurately predicting survival and guiding treatment in stage I and II hepatocellular carcinoma.

Accurately predicting survival in patients with early hepatocellular carcinoma (HCC) is essential for making informed decisions about treatment and prognosis. Herein, we have developed a machine learning (ML) model that can predict patient survival and guide treatment decisions. We obtained patient demographic information, tumor characteristics, and treatment details from the SEER database. To analyze the data, we employed a Cox proportional hazards (CoxPH) model as well as 3 ML algorithms: neural network multitask logistic regression (N-MLTR), DeepSurv, and random survival forest (RSF). Our evaluation relied on the concordance index (C-index) and Integrated Brier Score (IBS). Additionally, we provided personalized treatment recommendations regarding surgery and chemotherapy choices and validated models' efficacy. A total of 1136 patients with early-stage (I, II) hepatocellular carcinoma (HCC) who underwent liver resection or transplantation were randomly divided into training and validation cohorts at a ratio of 3:7. Feature selection was conducted using Cox regression analyses. The ML models (NMLTR: C-index = 0.6793; DeepSurv: C-index = 0.7028; RSF: C-index = 0.6890) showed better discrimination in predicting survival than the standard CoxPH model (C-index = 0.6696). Patients who received recommended treatments had higher survival rates than those who received unrecommended treatments. ML-based surgery treatment recommendations yielded higher hazard ratios (HRs): NMTLR HR = 0.36 (95% CI: 0.25-0.51, P < .001), DeepSurv HR = 0.34 (95% CI: 0.24-0.49, P < .001), and RSF HR = 0.37 (95% CI: 0.26-0.52, P = <.001). Chemotherapy treatment recommendations were associated with significantly improved survival for DeepSurv (HR: 0.57; 95% CI: 0.4-0.82, P = .002) and RSF (HR: 0.66; 95% CI: 0.46-0.94, P = .020). The ML survival model has the potential to benefit prognostic evaluation and treatment of HCC. This novel analytical approach could provide reliable information on individual survival and treatment recommendations.

Effects of fermented feed on growth performance, serum biochemical indexes, antioxidant capacity, and intestinal health of lion-head goslings.

Introduction: The aim of this study was to evaluate the effects of fermented feed on growth performance, antioxidant indexes and intestinal health in lion-head goslings. Methods: 288 male lion-head goslings (one-day-old) were randomly divided into four groups (6 replicates per group, 12 samples per replicate): control group (basal diet) and fermented feed (FF) groups (basal diet supplemented with 2.5, 5.0 and 7.5% FF, respectively). The experimental period lasted 28 days. Results: The results showed that 5.0 and 7.5% FF groups decreased feed conversion rate (FCR) when compared with the control group (p < 0.05). The 5.0% FF group reduced the activity of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum; while the 7.5% FF group decreased the concentration of total cholesterol (TC), ALP and LDH activity (p < 0.05). Furthermore, the 7.5% FF group significantly increased total antioxidant capacity (T-AOC) in serum (p < 0.05); 2.5% and 5.0% FF groups significantly increased glutathione peroxidase (GSH-Px) in serum (p < 0.05); all FF groups increased the activity of superoxide dismutase (T-SOD) in serum (p < 0.05). For intestinal health, the villous height and villi/crypt ratio in jejunum were increased in all FF groups, but crypt depth was decreased (p < 0.05); The 5.0% FF groups enhanced T-AOC activity in jejunum (p < 0.05); The 2.5% and 5.0% FF groups enhanced GSH-Px activity (p < 0.05) in jejunum; All FF groups reduced malondialdehyde (MDA) level in jejunum (p < 0.05). LEfSe analysis showed that the cecum microbiota was significantly dominant in the 2.5% FF group compared to the control group including Firmicutes, Lactobacillales, Lactobacillus, and Prevotella; the flora that were significantly dominant in the 5.0% FF group compared to the control group included Bacteroidaceae, Bacteroides, Megamonas, and Prevotella; and the groups that were significantly dominant in the 7.5% FF group compared to the control group included Bacteroidota, Bacteroides, Bacteroidaceae, and Ruminococcaceae. Discussion: In summary, dietary FF supplementation improved growth performance, serum biochemical parameters and antioxidant capacity of lion-head goslings, as well as improved jejunal tissue morphology and optimized intestinal flora structure. In particular, the FF addition at a dose of 7.5% was relatively more effective for lion- head goslings.

Increasing rate of hospitalization for severe peptic ulcer in digestive disease emergencies after the pandemic.

Since December 2019, the novel coronavirus has spread worldwide, affecting more than 510 million people, with more than 6 million deaths. However, some of the potential effects of the pandemic have not been thoroughly studied. We collected data from 2 regional emergency centers from May to November for the years 2015 to 2019, before the pandemic, and from May to November 2020, after the pandemic. We evaluated the incidence of each major type of digestive disease before and after the pandemic in adults at the 2 hospitals, which experienced coronavirus disease 2019 outbreaks with varying severity. A total of 11,394 patients were enrolled in the study Affiliated Hospital of Putian University (PUTIAN, n = 5503) Union Hospital, Tongji Medical college, Huazhong University of Science and Technology (UNION, n = 5891), and the proportion of male patients was approximately the same at both hospitals, with 3360 (61.1%) and 3680 (62.5%), respectively. The average ages of the patients were 55.8 ±â€…18.4 years PUTIAN and 54.3 ±â€…15.8 years UNION. The numbers of patients at the 2 hospitals increased steadily, but in 2020, the number of patients at UNION declined. The baseline characteristics of the 2 groups at the 2 hospitals showed significant differences for age before and after the pandemic but not for sex. The constituent ratios of diseases in each year in the 2 hospitals differed. The number of patients with peptic ulcers in 2020 was significantly different from those in each year from 2015 to 2019 (PUTIAN 2015-2020, 15.0%, 18.2%, 14.9%, 16.9%, 19.5%, 34.9%; UNION 2015-2020, 29.2%, 32.5%, 29.3%, 29.4%, 29.7%, 41.3%, respectively). The rates of peptic ulcer increased dramatically in both hospitals in 2020. An increase in the incidence of severe peptic ulcer was observed after the pandemic compared to the same period before the pandemic. Therefore, these factors should be considered in the formulation of public health strategies and the allocation of medical resources in the post pandemic era.

Can an incomplete ERAS protocol reduce postoperative complications compared with conventional care in laparoscopic radical resection of colorectal cancer? A multicenter observational cohort and propensity score-matched analysis.

Background: The patients undergoing laparoscopic radical colorectomy in many Chinese hospitals do not achieve high compliance with the ERAS (enhanced recovery programs after surgery) protocol. Methods: The clinical data from 1,258 patients were collected and divided into the non-ERAS and incomplete ERAS groups. Results: A total of 1,169 patients were screened for inclusion. After propensity score-matched analysis (PSM), 464 pairs of well-matched patients were generated for comparative study. Incomplete ERAS reduced the incidence of postoperative complications (p = 0.002), both mild (6.7% vs. 10.8%, p = 0.008) and severe (3.2% vs. 6.0%, p = 0.008). Statistically, incomplete ERAS reduced indirect surgical complications (27,5.8% vs. 59, 12.7) but not local complications (19,4.1% vs. 19, 4.1%). The subgroup analysis of postoperative complications revealed that all patients benefited from the incomplete ERAS protocol regardless of sex (male, p = 0.037, 11.9% vs. 17.9%; female, p = 0.010, 5.9% vs. 14.8%) or whether neoadjuvant chemotherapy was administered (neoadjuvant chemotherapy, p = 0.015, 7.4% vs. 24.5%; no neoadjuvant chemotherapy, p = 0.018, 10.2% vs. 15.8%). Younger patients (<60 year, p = 0.002, 7.6% vs. 17.5%) with a low BMI (<22.84, 9.4% vs. 21.1%, p < 0.001), smaller tumor size (<4.0 cm, 8.1% vs. 18.1%, p = 0.004), no fundamental diseases (8.8% vs. 17.0%, p = 0.007), a low ASA score (1/2, 9.7% vs. 16.3%, p = 0.004), proximal colon tumors (ascending/transverse colon, 12.2% vs. 24.3%, p = 0.027), poor (6.1% vs. 23.7%, p = 0.012)/moderate (10.3% vs. 15.3%, p = 0.034) tumor differentiation and no preoperative neoadjuvant radiotherapy (10.3% vs. 16.9%, p = 0.004) received more benefit from the incomplete ERAS protocol. Conclusion: The incomplete ERAS protocol decreased the incidence of postoperative complications, especially among younger patients (<60 year) with a low BMI (<22.84), smaller tumor size (<4.0 cm), no fundamental diseases, low ASA score (1/2), proximal colon tumors (ascending/transverse colon), poor/moderate differentiation and no preoperative neoadjuvant radiotherapy. ERAS should be recommended to as many patients as possible, although some will not exhibit high compliance. In the future, the core elements of ERAS need to be identified to improve the protocol.

One-step laparoscopic pancreatic necrosectomy verse surgical step-up approach for infected pancreatic necrosis: a case-control study.

BACKGROUND: The surgical step-up approach often requires multiple debridements and might not be suitable for infected pancreatic necrosis (IPN) patients with various abscesses or no safe route for percutaneous catheter drainage (PCD). This case-control study aimed to investigate the safety and effectiveness of one-step laparoscopic pancreatic necrosectomy (LPN) in treating IPN. METHODS: This case-control study included IPN patients undergoing one-step LPN or surgical step-up in our center from January 2015 to December 2020. The short-term and long-term complications after surgery, length of hospital stay, and postoperative ICU stays in both groups were analyzed. Univariate and multivariate logistic regression analyses were performed to explore the risk factors of major complications or death. RESULTS: A total of 53 IPN patients underwent one-step LPN and 37 IPN patients underwent surgical step-up approach in this study. There was no significant difference in the incidence of death, major complications, new-onset diabetes, or new-onset pancreatic exocrine insufficiency between the two groups. However, the length of hospital stay in the one-step LPN group was significantly shorter than that in the surgical step-up group. Univariate regression analysis showed that the surgical approach (one-step/step-up) was not the risk factor for major complications or death. Multivariate logistic regression analysis indicated that computed tomography (CT) severity index, American Society of Anesthesiologists (ASA) class IV, and white blood cell (WBC) were the significant risk factors for major complications or death. CONCLUSION: One-step LPN is as safe and effective as the surgical step-up approach for treating IPN patients, and reduces total hospital stay.

An Adaptive Learning Image Denoising Algorithm Based on Eigenvalue Extraction and the GAN Model.

This paper proposes a self-adjusting generative confrontation network image denoising algorithm. The algorithm combines noise reduction and the adaptive learning GAN model. First, the algorithm uses image features to preprocess the image and extract the effective information of the image. Then, the edge signal is classified according to the threshold value to suppress the problem of "excessive strangulation," and then the edge signal of the image is extracted to enhance the effective signal in the high-frequency signal. Finally, the algorithm uses an adaptive learning GAN model to further train the image. Each iteration of the generator network is composed of three stages. And then, we get the best value. Through experiments, it can be seen from the data that the article algorithm is compared with the traditional algorithm and the literature algorithm. Under the same conditions, the algorithm can ensure the operating efficiency while having better fidelity, and it can still denoise at the same time. The edge signal of the image is preserved and has a better visual effect.

A reciprocal feedback between N6-methyladenosine reader YTHDF3 and lncRNA DICER1-AS1 promotes glycolysis of pancreatic cancer through inhibiting maturation of miR-5586-5p.

BACKGROUND: Glycolysis is a pivotal process in metabolic reprogramming of tumorigenesis. Previous research has indicated that lncRNAs might play crucial roles in glycolysis of various tumors. However, the function of lncRNAs in glycolysis of pancreatic cancer has not been fully elucidated. METHODS: Bio-information analyses were applied to reveal the potential glycolysis-associated lncRNA. RT-PCR and fluorescence in situ hybridization (FISH) assays were applied to detect the expression of antisense RNA1 of DICER1 (DICER1-AS1) in pancreatic cancer tissues and cell lines. Gain- and loss-of-function experiments were performed to evaluate the roles of DICER1-AS1 in glycolysis and tumorigenesis of PC. Mechanistic experiments including luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) were employed to uncover the downstream targets and regulatory mechanism of DICER1-AS1 in glycolysis of PC. RESULTS: Bio-information analysis indicated that DICER1-AS1 was downregulated in PC and negatively correlated with glycolytic genes expression. Meanwhile, overexpression of DICER1-AS1 inhibited glycolysis, proliferation, and metastasis of PC cells both in vitro and in vivo. Mechanistically, DICER1-AS1 promoted transcription of its sense gene DICER1 by recruiting transcriptional factor YY1 to the DICER1 promoter. Meanwhile, DICER1 promoted maturation of miR-5586-5p which consequently inhibited glycolytic gene expression including LDHA, HK2, PGK1, and SLC2A1. Notably, enhanced interaction between N6-methyladenosine (m6A) reader YTHDF3 and DICER1-AS1 led to degradation of DICER1-AS1 in response to glucose depletion. Moreover, our data revealed that YTHDF3 was a critical target for miR-5586-5p, by which forming a negative feedback with DICER1-AS1 to regulate glycolysis of PC. CONCLUSION: Our results implicate a negative feedback of m6A reader YTHDF3 and glycolytic lncRNA DICER1-AS1 is involved in glycolysis and tumorigenesis of PC.

A reciprocal feedback of miR-548ac/YB-1/Snail induces EndMT of HUVECs during acidity microenvironment.

BACKGROUND: Researches indicated the process of Endothelial-Mesenchymal-Transition (EndMT) of vascular endothelial cells (ECs) was critically involved in the progression of tumor. ECs demonstrated functional and phenotypic heterogeneity when located under different microenvironments. The extracellular pH of tumor tissues was acidic compared to that of normal tissues. However, there was still unclear whether the acidic microenvironment affected the EndMT of vascular ECs. METHODS: Human Umbilical Vein Endothelial Cell (HUVECs) was cultured under the normal or acidic medium to evaluate the alteration of morphology, migration, permeability, and EndMT markers. Microarray assay was adopted to analyze the differential expression of miRNAs in the acidity-treated HUVECs. Gain- and loss- of function experiments were performed to evaluate the functional role of miRNA-548ac on acidity-induced EndMT of HUVECs. Luciferase reporter and Chromatin-immunoprecipitation assays were conducted to assess the downstream pathway of miRNA-548ac in acidity-induced EndMT of HUVECs. RESULTS: Our results showed that HUVECs demonstrated mesenchymal transition under acidic conditions with the increase of migration, permeability, and expression of α-SMA and Vimentin, but the expression of vascular endothelial cadherin (VE-cadherin) and CD31 were reduced. In addition, the acidity-treated HUVECs remarkably facilitated the transmigration of pancreatic cancer cells. The expression of miRNA-548ac was significantly decreased in the acidity-treated HUVECs. Moreover, overexpression of miR-548ac inhibited the EndMT of HUVECs and consequently impeded the transmigration of pancreatic cancer cells. The miR-548ac inhibited the expression of YB-1 by binding to the 3'UTR of its mRNA, and YB-1 promoted the translation of Snail which was a critical regulator of EndMT. What's more, Snail transcriptionally inhibited the expression of miR-548ac through binding to the promoter of its host gene. CONCLUSIONS: Our data implicated that the acidic microenvironment promoted the EndMT of HUVECs by the miR-548ac/YB-1/Snail axis, which could contribute to the metastasis of pancreatic cancer.

PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1.

Rationale: PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. Methods: A series of experiments in vitro and in vivo were conducted to reveal the role of PLAGL2 in GC progression. Results: The data revealed that PLAGL2 promotes GC cell proliferation, migration, invasion, and EMT in vitro and in vivo. Mechanistically, we demonstrated the critical role of PLAGL2 in the stabilization of snail family transcriptional repressor 1 (Snail1) and promoting Snail1-mediated proliferation and migration of GC cells. PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly. In addition, GSK-3ß-dependent phosphorylation of Snail1 protein is essential for USP37-mediated Snail1 deubiquitination regulation. Conclusions: In general, PLAGL2 promotes the proliferation and migration of GC cells through USP37-mediated deubiquitination of Snail1 protein. This work provided potential therapeutic targets for GC treatment.

TM4SF1 promotes EMT and cancer stemness via the Wnt/ß-catenin/SOX2 pathway in colorectal cancer.

BACKGROUND: Transmembrane 4 L six family member 1 (TM4SF1) is upregulated in several epithelial cancers and is closely associated with poor prognosis. However, the role of TM4SF1 and its potential mechanism in colorectal cancer (CRC) remain elusive. METHODS: We investigated the expression of TM4SF1 in the Oncomine, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of CRC tissues. The effect of TM4SF1 on the epithelial-to-mesenchymal transition (EMT) and cancer stemness of CRC cells was investigated by Transwell, wound healing and sphere formation assays. A series of in vitro and in vivo experiments were conducted to reveal the mechanisms by which TM4SF1 modulates EMT and cancer stemness in CRC. RESULTS: TM4SF1 expression was markedly higher in CRC tissues than in non-tumour tissues and was positively correlated with poor prognosis. Downregulation of TM4SF1 inhibited the migration, invasion and tumour sphere formation of SW480 and LoVo cells. Conversely, TM4SF1 overexpression significantly enhanced the migration, invasion and tumoursphere formation potential of CRC cells, Additionally, TM4SF1 silencing inhibited the EMT mediated by transforming growth factor-ß1 (TGF-ß1). Mechanistically, gene set enrichment analysis (GSEA) predicted that the Wnt signalling pathway was one of the most impaired pathways in TM4SF1-deficient CRC cells compared to controls. The results were further validated by WB, which revealed that TM4SF1 modulated SOX2 expression in a Wnt/ß-catenin activation-dependent manner. Furthermore, we found that knockdown of TM4SF1 suppressed the expression of c-Myc, leading to decreased c-Myc binding to the SOX2 gene promoter. Finally, depletion of TM4SF1 inhibited metastasis and tumour growth in a xenograft mouse model. CONCLUSION: Our study substantiates a novel mechanism by which TM4SF1 maintains cancer cell stemness and EMT via the Wnt/ß-catenin/c-Myc/SOX2 axis during the recurrence and metastasis of CRC.

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer.

Rationale: Previous studies have reported on the role of extracellular acidity in the metastasis of numerous cancers. However, the involvement of long noncoding RNA (lncRNA) in the extracellular acidity-induced cancer metastasis of pancreatic cancer (PC) remains unclear. Methods: Different expression levels of lncRNAs in PC cells under normal and acidic conditions were compared by RNA sequencing (RNA-seq). The effects of antisense lncRNA of metastasis suppressor 1 (MTSS1-AS) on acidic PC cells were assessed by gain- and loss-of-function experiments. Fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down, Western blot, luciferase reporter, and Chromatin immunoprecipitation assays were employed to determine the regulatory mechanisms of MTSS1-AS in the acidity-induced metastasis of PC cells. The expression of MTSS1-AS and associated pathways were compared in PC samples and peritumoral normal tissues. Results: RNA-seq demonstrated that MTSS1-AS was significantly downregulated in pancreatic cells cultured with the acidic medium. The overexpression of MTSS1-AS remarkably inhibited the acidity-promoted metastasis of PC cells by upregulating the expression of its sense gene metastasis suppressor 1 (MTSS1). Mechanistically, MTSS1-AS scaffolded the interaction between E3 ubiquitin-protein ligase STIP1 homology and U-box containing protein 1 (STUB1) and transcription regulator myeloid zinc finger 1 (MZF1), leading to ubiquitination-mediated degradation of MZF1. Further, MZF1 inhibited the expression of MTSS1 by binding to the MTSS1 promoter. Thus, the acidity-reduced MTSS1-AS facilitated the stability of MZF1 and its inhibitory effect on MTSS1 transcription, thereby promoting the metastasis of PC cells under acidic conditions. Moreover, MTSS1-AS was transcriptionally repressed by the binding of MYC proto-oncogene (Myc) with initiator (Inr) elements of the MTSS1-AS promoter. Meanwhile, MTSS1-AS mutually repressed the expression of Myc by impairing the MZF1-mediated transcription activation of Myc, thereby forming a negative feedback loop between MTSS1-AS and Myc in acidic PC cells. In accordance with the experimental results, MTSS1-AS and MTSS1 were downregulated in PC and correlated with poor overall survival. Conclusions: The results implicated that a reciprocal feedback loop between Myc and MTSS1-AS contributed to the extracellular acidity-promoted metastasis of PC, and indicated that MTSS1-AS was a valuable biomarker and therapeutic target for PC.

The effect of emergency surgery on acute abdomen patients with COVID-19 pneumonia: a retrospective observational study.

During the COVID-19 outbreak, some patients with COVID-19 pneumonia also suffered from acute abdomen requiring surgical treatment; however, there is no consensus for the treatment of such patients. In this study, we retrospectively reviewed 34 patients with acute abdomen who underwent emergency surgery during the COVID-19 outbreak. Among the 34 patients with acute abdomen, a total of six cases were found with COVID-19 pneumonia (clinical classification for COVID-19 pneumonia: all were the common type). On the premise of similar demographics between both groups, patients with COVID-19 pneumonia had worse indicators of liver and coagulation function. Compared with acute abdomen patients without COVID-19, patients with COVID-19 pneumonia had a longer hospital stay, but there were no significant differences in postsurgical complications (P = 0.58) or clinical outcomes (P = 0.56). In addition, an obvious resolution of lung inflammation after surgery was observed in five COVID-19 patients (83.3%). No new COVID-19 cases occurred during the patients' hospital stays. Therefore, for the common type of COVID-19 pneumonia, emergency surgery could not only improve the outcomes of COVID-19 pneumonia patients with acute abdomen, but also benefit the resolution of pulmonary inflammation.

MicroRNA-214-3p targets the PLAGL2-MYH9 axis to suppress tumor proliferation and metastasis in human colorectal cancer.

Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.

PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via ß-catenin-dependent regulation of ZEB1.

BACKGROUND: We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal cancer (CRC) remain largely unknown. METHODS: Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC. RESULTS: Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of ß-catenin by decreasing its phosphorylation. The depletion of ß-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells. CONCLUSIONS: Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal cancer metastasis via ß-catenin-dependent regulation of ZEB1.

Increased miR-214 expression suppresses cell migration and proliferation in Hirschsprung disease by interacting with PLAGL2.

BACKGROUND: The miR-214 has been reported to be associated with various diseases, but its involvement in the pathophysiology of Hirschsprung disease (HSCR) is almost completely unexplored. METHODS: In our study, we conducted a series of experiments to unravel the biological role of miR-214 in the pathophysiology of HSCR. qRT-PCR and western blotting were utilized to investigate the relative expression levels of miR-214, mRNAs, and proteins of related genes in colon tissues from 20 controls without HSCR and 24 patients with HSCR. The potential biological role of miR-214 in two cell lines (SKN-SH and SH-SY5Y) was assessed using the CCK8 assay, EdU staining, transwell assay, and flow cytometry. The dual-luciferase reporter assay was used to confirm PLAGL2 as a common target gene of miR-214. RESULTS: All results suggested that miR-214 is upregulated in HSCR tissue samples compared with controls. Additionally, we found that miR-214 could inhibit cell proliferation and migration by directly downregulating the expression of PLAGL2, and the extent of the miR-214-mediated inhibitory effects could be rescued by a PLAGL2 overexpression plasmid. CONCLUSION: Our results revealed that miR-214 is indeed involved in the pathophysiology of HSCR and suppresses cell proliferation and migration by directly downregulating PLAGL2 in cell models.

Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer.

Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play an important role in the metastasis and chemoresistance in the context of colorectal cancer (CRC). Downregulation of death associated protein kinase 1 (DAPK1) may promote metastasis and chemoresistance of cancer cells through various mechanisms. However, the association between DAPK1 and CSCs or EMT has not been explored. In this study, we demonstrated that DAPK1 was associated with elevated stemness of CSCs in patients with CRC. Silencing of DAPK1 in CRC cell lines promoted the metastasis and chemoresistance due to increased stemness of CSCs and enhanced mesenchymal phenotype, an effect that was mediated via activation of the transcription factor, zinc finger E-box binding homeobox 1 (ZEB1). Blockade of this signaling pathway attenuated the stemness of CSCs and rescued the EMT process. DAPK1-ZEB1 may lie at the interface of TGF-ß and WNT pathways and participate in both CSCs and EMT process. Targeted therapies aimed at DAPK1-ZEB1 pathway may inhibit the chemoresistance and metastasis of CRC. KEY MESSAGES: Downregulation of DAPK1 promotes chemoresistance and metastasis of CRC. Inhibition of DAPK1 promotes the stemness of cancer stem cells and EMT process. DAPK1-ZEB1 may lie at the interface of TGF-ß and WNT pathways. DAPK1-ZEB1 participates in both CSCs and EMT process.