ENO1 contributes to the gemcitabine resistance of pancreatic cancer through the YAP1 signaling pathway.

Pancreatic cancer (PC), a leading cause of cancer-related deaths, has a 5-year survival rate of approximately 10%. α-Enolase (ENO1) is a junction channel protein involved in tumor cell apoptosis and chemoresistance. However, the role of ENO1 in PC remains unclear. The expression and prognosis of ENO1 levels were determined in PC using public databases based on The Cancer Genome Atlas (TCGA) data sets. Cell viability, half maximal inhibitory concentration (IC50), autophagy, apoptosis, and autophagy markers were examined using cell counting kit-8 (CCK-8), transmission electron microscope, flow cytometry assays, and immunoblot, respectively. Using the Gene Expression Omnibus (GEO) and TCGA data sets, we found that ENO1 was significantly enriched in PC tumor tissues, and high expression levels of ENO1 were associated with an unfavorable prognosis. Whereas ENO1 silencing suppressed proliferation, autophagy, and induced cell apoptosis in PC cells, and inhibited tumor growth in vivo. Mechanistically, knockdown of ENO1 enhanced cellular cytotoxicity of gemcitabine (GEM), as well as reducing the expression of yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway in vitro. YAP1 promoted autophagy and protected PC cells from GEM-induced apoptotic cell death. Furthermore, YAP1 overexpression attenuated the inhibition effects of ENO1 silencing. Our results suggest that ENO1 overexpression promotes cell growth and tumor progression by increasing the expression of YAP1 in PC. Further studies are required to understand the detailed mechanisms between ENO1 and YAP1 in PC.

MiR-485-3p/MiR-543/MiR-337-3p is Required for the Oncogenic Potential of the Hsa_circ_0007385-MEMO1 Axis in Colorectal Cancer.

Circular RNAs (circRNAs) play regulatory roles in the biological processes of multiple tumors, colorectal cancer (CRC) included. Our previous study probed the impact of circ_0007385 on CRC cell malignant behaviors, while the underlying mechanism remains obscure. In this work, the potential mechanism of hsa_circ_0007385 in CRC was probed. Functional experiments were implemented for probing the function of hsa_circ_0007385 in CRC. Further analysis revealed the relation between hsa_circ_0007385 and miRNAs. A xenograft mouse model was implemented for probing the influence of hsa_circ_0007385 on CRC growth and metastasis in vivo. Hsa_circ_0007385 was up-regulated in CRC. Hsa_circ_0007385 positively regulated its host gene mediator of cell motility 1 (MEMO1). Hsa_circ_0007385 silencing inhibited CRC progression. Hsa_circ_0007385 and MEMO1 bond to miR-485-3p/miR-543/miR-337-3p, and these three miRNAs were lowly expressed in CRC, and negatively modulated by hsa_circ_0007385. Hsa_circ_0007385 functioned as an oncogene in CRC in a miR-485-3p/miR-543/miR-337-3p- or MEMO1-dependent manner. Hsa_circ_0007385 promoted CRC progression via modulating miR-485-3p/miR-543/miR-337-3p/MEMO1 axis. Thus, circ-MEMO1 might be a promising therapeutic target for CRC.

Overexpression of DAPK1-mediated inhibition of IKKß/CSN5/PD-L1 axis enhances natural killer cell killing ability and inhibits tumor immune evasion in gastric cancer.

Gastric cancer (GC) originates from the stomach and is a prevalent human malignancy. Dysfunction of death associated protein kinase 1 (DAPK1) has been identified as a major regulator involved in the development and progression of GC. However, there's limited data regarding the regulatory mechanism of GC. Herein, we investigated role of DAPK1 in natural killer (NK) cell killing ability and immune evasion of GC cells and mediated pathway. Samples from GC-related gene expression profile and clinical samples from 67 patients with GC were collected to determine the expression of DAPK1, IκB kinase ß (IKKß), programmed death receptor-ligand 1 (PD-L1), and photomorphogenesis 9 (COP9) signalosome 5 (CSN5). The binding affinity among DAPK1, IKKß, CSN5, and PD-L1 was characterized to verify the underlying mechanism. GC lines were transfected with overexpressed plasmid or siRNA to determine the effect of DAPK1/IKKß/CSN5/PD-L1 axis on NK cell killing ability and immune evasion of GC cells. GC cells and tissues presented low expression of DAPK1 and high expression of IKKß, CSN5 and PD-L1. IKKß, negatively regulated by DAPK1, was capable of activating CSN5 and upregulating PD-L1 expression. Overexpression of DAPK1 promoted NK cell killing ability and reduced immune evasion, coupled with reduction of NK cell apoptosis and increases in levels of TNF-α, IFN-γ, CD107a, and Granzyme B cytokines. The tumor-suppressing properties of DAPK1 through downregulation of IKKß/CSN5/PD-L1 axis in GC were further confirmed in vivo. In summary, overexpression of DAPK1 promoted the NK cell killing ability and restrained immune evasion of GC cells, providing a potential therapeutic strategy for GC treatment by modulating immune evasion.

Circular RNA circ_0065378 upregulates tumor suppressor candidate 1 by competitively binding with miR-4701-5p to alleviate colorectal cancer progression.

BACKGROUND AND AIM: Colorectal cancer (CRC), the third most lethal human cancer worldwide, seriously threatens human health and life. Numerous circular RNAs (circRNAs) including circ_PLXNB1 (hsa_circ_0065378) have been confirmed to be dysregulated in CRC by RNA-seq analysis. We aimed to explore the functional role of circ_PLXNB1 in CRC malignant behaviors and clarify its potential molecular mechanism. METHODS: Gene expression levels of circ_PLXNB1 and miR-4701-5p were determined by quantitative real-time polymerase chain reaction analysis. MTT and Transwell assays were conducted to measure cell proliferation, invasion, and migration. Protein expression of tumor suppressor candidate 1 (TUSC1), E-cadherin and N-cadherin was determined by western blot analysis. Mouse xenograft models were used to investigate the role of circ_PLXNB1 in tumor growth. RESULTS: The results showed that gene expression of circ_PLXNB1 in CRC tissues was significantly downregulated. Overexpression of circ_PLXNB1 inhibited the malignant behaviors of CRC cells, as manifested by the decrease in cell proliferation, cell invasion, migration, and EMT. Mechanistically, circ_PLXNB1 exerted its functional effects by binding with miR-4701-5p. Moreover, TUSC1 siRNA partially abolished the suppressive effect of the miR-4701-5p inhibitor or circ_PLXNB1 on CRC cell malignant behaviors. CONCLUSIONS: Circ_PLXNB1 attenuated CRC progression by binding with miR-4701-5p to overexpress TUSC1, indicating that the circ_PLXNB1/miR-4701-5p/TUSC1 axis might be a potential novel molecular target in CRC diagnosis and therapy.

Silencing PFKP restrains the stemness of hepatocellular carcinoma cells.

BACKGROUND: Glycolysis reprogramming is deeply involved in the progression of hepatocellular carcinoma (HCC), in which HCC cells with stemness traits play important roles as well. Thus, whether platelet isoform of phosphofructokinase 1 (PFKP), a rate-limiting enzyme in glycolysis, contributes to the maintenance of stemness of HCC cells is worth investigation. METHODS: PFKP levels were compared between human hepatocellular carcinoma and adjacent normal tissues by Western blotting and immunohistochemistry. The relationship between PFKP expression and clinic pathological features was also analyzed. Furthermore, the colony formation capabilities and the levels of stemness markers (ALDH1, CD44, CD133, Sox-2) as well as ß-catenin were compared between HCC cells either undergoing PFKP silencing or overexpression. RESULTS: PFKP levels were higher in HCC as compared to normal hepatic tissues. Silencing PFKP decreased HCC proliferation, colony formation capabilities, and levels of stemness markers and ß-catenin; whereas overexpressing PFKP demonstrated the opposite effects. CONCLUSION: PFKP promoted HCC proliferation and contributed to the maintenance of HCC stemness. Silencing PFKP could restrain the stemness of HCC, suggesting that PFKP may be a potential therapeutic target for HCC treatment.

Clinical application of pancreatic-duct-jejunum end-to-side continuous suture anastomosis in total laparoscopic pancreaticoduodenectomy.

BACKGROUND: To present a new pancreaticojejunostomy technique for laparoscopic pancreaticoduodenectomy (LPD) and to evaluate its safety and reliability. METHODS: The data of 120 patients who underwent LPD at a single centre from October 2017 to October 2019 were retrospectively analysed. Of these patients, 71 received continuous suture pancreaticojejunostomy, and 49 received "8-character" suture pancreaticojejunostomy for LPD. We compared and analysed the operation time, anastomosis time, and incidence of postoperative complications between the patients in the two groups. RESULTS: All operations were successfully performed, with no transfer to open surgery. The operation time and anastomosis time in the continuous suture group were lower than those in the "8-character" suture group (305.8 ± 60.7 min vs. 354.3 ± 69.1 min; 28.6 ± 6.3 min vs. 39.4 ± 11.9 min P < 0.001), and the postoperative hospital stay was also shorter (12.9 ± 3.8 days vs. 15.4 ± 5.8 days P < 0.05) in the continuous suture group. There was no significant difference in the pancreatic duct diameter or intraoperative blood loss between the two groups. There was also no significant difference in the incidence of a pancreatic fistula between the continuous suture group and the "8-character" suture group. The data of patients in the continuous suture group with pancreatic duct diameters < 3 mm and ≥ 3 mm were statistically analysed. There was no significant difference in the operation time, pancreaticojejunostomy time, postoperative hospital stay, or incidence of pancreatic fistula in the different pancreatic duct diameter groups. CONCLUSIONS: Continuous suture of pancreaticojejunostomy in LPD is simple, safe, reliable, and rapid. This technique not only saves the anastomosis time but also suitable for pancreatic ducts < 3 mm.

Billroth II anastomosis maintains SMI and BMI better than Roux-en-Y anastomosis following totally laparoscopic distal gastrectomy: a propensity score-matched study.

BACKGROUND: Gastric cancer is a major public health problem around the globe. With the standardization of tumor treatment, surgery continues to be the most important treatment method for gastric cancer. However, changes in body composition and nutrition index parameters in patients with Billroth II and Roux-en-Y anastomosis following totally laparoscopic distal gastrectomy (TLDG) remain unclear. METHODS: This was a single-center retrospective study. A total of 369 patients who underwent TLDG at the First Affiliated Hospital of Soochow University (Suzhou, China) between January 2016 and February 2019 were included and assigned to the Billroth II group or Roux-en-Y group according to the anastomosis method. After propensity score matching, body composition and relevant clinical data were compared between the two groups. RESULTS: The operation time for the Billroth II group was significantly shorter than for the Roux-en-Y group (174.12 ± 39.33 min vs. 229.19 ± 28.12 min, P < 0.001). In addition, the Billroth II group showed lower skeletal muscle loss. Specifically, the Billroth II group showed a - 4.77 ± 4.88% change in the skeletal muscle index (SMI), whereas the Roux-en-Y group showed a - 11.89 ± 8.68% change (P = 0.001). The Billroth II group also showed a smaller decrease in BMI than the Roux-en-Y group (- 6.67 ± 7.76% vs. - 13.12 ± 10.79%, P = 0.018). CONCLUSIONS: These results suggest that Billroth II anastomosis after TLDG has advantages over Roux-en-Y for maintaining patient body composition, especially in terms of SMI, and may serve as a useful reference when choosing an anastomosis method.

The effect and clinical significance of FN1 expression on biological functions of gastric cancer cells.

Fibronectin 1 (FN1) is a glycoprotein molecule widely distributed in cell structures such as smooth muscle cell layer, vascular cell membrane and nerve cell layer. It participates in cell adhesion, migration and movement of various cells. In recent years, FN1 has been shown to play an important role in the regulation of various malignant tumors such as lung cancer, colorectal cancer, and ovarian cancer. However, its regulation and mechanism of action in gastric cancer have been rarely reported, and these are also associated with some controversy. The aim of this study was to investigate the clinical significance of FN1 in gastric cancer, to study the effects of FN1 on proliferation, apoptosis, migration and invasion of GC cells, and the mechanisms involved. The expression of FN1 in gastric cancer tissues was determined using immunohistochemistry staining. The comparative expression levels of FN1 were assayed with RT-PCR and Western blotting. The correlation amongst FN1 expression, clinicopathological parameters and prognosis of gastric cancer patients was determined. Cell transfection was used to silenceFN1 expression in gastric cancer cells. Plate cloning and CCK-8 assays were used to determine cell proliferation, while apoptosis was assayed with flow cytometry. Cell migration and invasion was measured with transwell assay. The expressions of EMT-related proteins were assayed using western blotting. The results showed that FN1 was upregulated in GC tissues and cell lines, and its expression level was closely related to tumor invasion, TNM stage, lymph node metastasis and survival. Inhibition of FN1 expression significantly reduced proliferation, migration, invasion and EMT processes of GC cells, and enhanced cell apoptosis. These results confirm that FN1 is up-regulated in GC, thereby functioning as an oncogenic gene. The high expression of FN1 might affect the clinicopathological parameters and prognosis of gastric cancer patients.

Longer Operating Time During Gastrectomy Has Adverse Effects on Short-Term Surgical Outcomes.

BACKGROUND: Gastric cancer continues to be one of the malignant tumor types with high morbidity and mortality worldwide. Although remarkable improvements have been made to combat gastric cancer, surgery is still the first choice of treatment for gastric cancer. METHODS: This was a single-center and retrospective study. A total of 110 patients who underwent radical gastrectomy with D2 lymph node dissection between 2014 and 2017 were included in this study, and all patients were treated by the same medical staff. Based on the median operating time, patients were grouped into a long-time group (>180 min) and a short-time group (≤180 min). Influences of operating time on outcomes of patients in the short-term and long-term groups were analyzed. RESULTS: The long-time group showed a higher incidence of postoperative complications compared with the short time group (P < 0.01) with a significant decrease in serum albumin and the prognostic nutritional index value. Moreover, a long operating time was often caused by the operating start time (P < 0.001), excision difficulty caused by lager tumor size (P < 0.001), worse tumor differentiation, and deeper tumor invasion (P < 0.05). However, length of operating time did not significantly influence overall survival of patients who underwent radical gastrectomy. CONCLUSIONS: The results suggested that operating time might be an indicator of the incidence of postoperative complication and that several important variables, such as prognostic nutritional index, serum albumin, operating start time, and excision time, could be intervened in the perioperative period to help patients gain a better outcome after gastrectomy.

The influence of aberrant expression of GLI1/p-S6K on colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have reported that PI3K/AKT/mTOR pathway regulated the GLI1 expression level via SMO-independent pathway in a variety of tumor types. We detected the expression level of GLI1/p-S6K in CRC tissues. We found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression. Moreover, GLI1 and p-S6K expression was considered to be independent prognostic factors in CRC patient and the positive co-expression of GLI1/p-S6K had greater influence than single expression positive on the prognosis of postoperative patients with tumor size≥5 cm, well differentiation, positive lymph node metastasis, venous invasion, neural invasion and TNM III-IV. Meanwhile, the GLI1/p-S6K expression had impact on more clinicopathologic features in colon-side carcinoma than in rectum-side carcinoma and the mTOR/S6K/GLI1 axis played an important role in CRC especially in advanced stage. Hence, further studies are underway to explore the molecular mechanism between GLI1 and p-S6K in CRC, and in addition, it offers novel facilities for molecular targeting therapy for CRC.

[Identification of the 1RS-7DS.7DL wheat-rye small segment translocation lines].

Rye (Secale cereale L., RR) is a valuable genetic resource for the improvement of common wheat (Triticum aestivum L., AABBDD). Transferring alien rye genes into wheat by distant hybridization and automatic chromosome doubling is an important and efficient method to boost agronomic traits, disease resistance and widening the gene pool in wheat. In this study, an octoploid triticale CD-13 (AABBDDRR) was obtained via automatic chromosome doubling by crossing landrace Penganbaimaizi (T. aestivum L., AABBDD) and rye "Qinling rye" (S. cereale cv. Qinling, RR). GISH and FISH analyses indicated that CD-13 contained a 1RS-7DS.7DL wheat-rye small segment translocation chromosome. In order to transfer the 1RS-7DS small segment translocation into hexaploid wheat, 58 lines of the F5 inbred population from the cross CD-13 x Chuanmai 42 were screened for rye chromosome segments by GISH and FISH analyses. The results showed that 13 lines contained the 1RS-7DS.7DL small segment translocation chromosome by reciprocal translocation between 1RS and 7DS. These translocation lines carrying 1RS small rye alien segment were tested for the translocation breakpoints and the presence of a storage protein locus Sec-1. The Sec-1 locus was absent in the line 811, a stable 1RS-7DS.7DL small segment translocation line. The translocation breakpoint of 1RS-7DS.7DL of this line was located in the interval of IB267-IAG95 around the telomere of 1RS chromosome. Thousand-kernel weight of the line 811 was much higher than the parent CD-13, but not significantly different from Chuanmai 42. This indicated that 1RS-7DS.7DL small segment translocation had no negative effect on thousand-kernel weight in the genetic background of Chuanmai 42. The line with 1RS-7DS.7DL translocation chromosomes can be used as a new genetic material for further studies of valuable genes and their genetic effect on 1RS small segment.

Decoy receptor 3 (DcR3) overexpression predicts the prognosis and pN2 in pancreatic head carcinoma.

BACKGROUND: This study was carried out to examine decoy receptor 3 (DcR3) expression and investigate its clinical and prognostic significance in patients with pancreatic head carcinoma. METHODS: Tissue samples were obtained from 50 patients with pancreatic head carcinoma. DcR3 protein expression in tissues and sera was assessed by immunohistochemistry and ELISA. Correlations between DcR3 and clinicopathologic features and prognoses were analyzed statistically. RESULTS: Serum DcR3 levels were significantly elevated in patients with pancreatic head carcinoma compared with patients with cystadenoma and healthy individuals (P < 0.01 and P < 0.01, respectively). DcR3 overexpression correlated with lymph node metastases and TNM stages (P < 0.05 and P < 0.05, respectively). Median overall survival for the high DcR3 group was 16.3 months, compared to 21.6 months for the low DcR3 group (P < 0.05). In the low DcR3 group, no significant difference was found in the overall survival between patients who underwent standard pancreatoduodenectomy (SPD) and those who had radical pancreatoduodenectomy (RPD) (P > 0.05). In the high DcR3 group, the median overall survival rates were 16.8 months in the RPD group and 13.5 months in the SPD group (P < 0.05). CONCLUSIONS: We found that DcR3 was overexpressed in pancreatic head carcinoma. The patients with high DcR3 levels had higher pN2 stages than those with low DcR3 levels. Detecting serum DcR3 level preoperatively might be an additional approach for evaluating pN2 stage and guiding the range of lymphadenectomy.

CircANXA4 (hsa_circ_0055087) regulates the miR-1256/PRM1 axis to promote tumor progression in colorectal cancer.

Colorectal cancer (CRC) incidence ranks third among malignant cancers with a high propensity for distant metastasis. Despite continuous efforts to improve treatment, the prognosis especially in patients with advanced distant metastasis is low. The mechanism of development and progression of CRC is not fully understood. Non-coding RNAs (ncRNAs) have emerged as essential regulators in cancer progression. Here, we aim to dissect the role of one critical ncRNA, circANXA4, in CRC progression. CircANXA4 expression was analyzed by the GEO database. Differentially expressed circRNAs were identified by the Limma package R software. Expression of circANXA4 and miR-1256 was detected by qRT-PCR. The regulation of circANXA4 on cell proliferation and progression was confirmed with the cell viability assay using cell counting kit-8 (CCK-8) and transwell migration assay. RNA pull-down assay, RNA immunoprecipitation (RIP), and western blot were used to determine the interaction between circANXA4, miR-1256, and protamine1 (PRM1). CircANXA4 was upregulated in both CRC tissues and cell lines. Knockdown of circANXA4 effectively reduced cell proliferation, progression, and migration. Additionally, silencing circANXA4 remarkably increased miR-1256 expression, while reducing PRM1 expression, thereby demonstrating that circANXA4 downregulates miR-1256 expression through a complementary binding site. Rescue experiments revealed the interactions between circANXA4, miR-1256, and PRM1. Pearson correlation analysis revealed that circANXA4 expression positively correlated with PRM1 expression and miR-1256 expression inversely correlated with PRM1 expression. In sum, we demonstrated that circANXA4 promotes cancer cell proliferation and progression by sponging miR-1256 and upregulating PRM1 in CRC.

Anti-Liver Fibrosis Role of miRNA-96-5p via Targeting FN1 and Inhibiting ECM-Receptor Interaction Pathway.

The aberrant expression of mRNAs participates in the pathogenesis of hepatic fibrosis. However, the precise mechanisms regulated by microRNAs (miRNAs) remain unclear. This study aims to investigate the functions about differentially expressed mRNAs (DEMs) in liver fibrosis and their regulatory mechanisms. The DEMs datasets about hepatic stellate cells (HSCs) obtained from hepatic fibrosis mice versus HSCs obtained from normal mice were downloaded from the GEO database (GSE120281). According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the GSE120281 datasets, ECM-receptor interaction was the most significant enrichment pathway that was correlated with hepatic fibrosis, and the fibronectin 1 (FN1) gene was upregulated most significantly in the signaling pathway. Downregulation of the expression of the FN1 gene by transfecting with FN1-siRNA alleviated the activity of HSCs. Four different bioinformatics web-based tools were used to predict that microRNA-96-5p (miR-96-5p) would directly target FN1, and a luciferase assay further confirmed this. Moreover, miR-96-5p was declined in activated HSCs and FN1, whereas laminin γ1 (LAMC1), collagen 1α1 (COL1A1) in the ECM-receptor interaction pathway, and the fibrosis marker α-smooth muscle actin (α-SMA) could be reduced by upregulation of the miRNA. Additionally, miR-96-5p expression was low in CCl4-induced liver fibrosis mice. Increased miR-96-5p expression alleviated liver fibrosis, improved liver function, and inhibited the expression of α-SMA, FN1, COL1A1, and LAMC1. In conclusion, this study indicated that upregulation of miR-96-5p could reduce HSC activation and relieve hepatic fibrosis by restraining the FN1/ECM-receptor interaction pathway.

Hsa-circ-0052001 promotes gastric cancer cell proliferation and invasion via the MAPK pathway.

BACKGROUND: Gastric cancer (GC) ranks fourth among the causes of death from malignant tumors in the world. Studies have implicated the dysregulation of circRNAs with GC. However, the relationship between hsa-circ-0052001 and GC is unclear. METHODS: In our current study, we assessed the expression levels of hsa-circ-0052001 in GC cells and tissues using quantitative real-time PCR (qPCR). The role of hsa-circ-0052001 expression on the proliferation and invasion of GC cells was assessed using in vitro experiments. The role of hsa-circ-0052001 on the proliferation of GC cells was also analyzed using in vivo models. The pathways downstream of hsa-circ-0052001 were identified using bioinformatics analyses, western blot (WB) assays, and qRT-PCR. RESULTS: We found that compared with normal gastric mucosa epithelial cells and adjacent paracancer tissues, hsa-circ-0052001 was overexpressed in GC cells and tissues. Also, the hsa-circ-0052001 level was linked to patient clinicopathological characteristics of GC. Cell proliferation and metastatic ability were inhibited in gastric cancer cells when hsa-circ-0052001 was knocked down in vitro and cancer growth in vivo. Mechanistically, hsa-circ-0052001 promoted the carcinogenesis of GC cells via the MAPK signal pathway. CONCLUSION: Hsa-circ-0052001 functions as a tumor gene in promoting the progression of GC through MAPK pathway, which has provided a promising target for patients with GC.

Constructing oriented two-dimensional fish scale-like Gd@MXene barrier walls in polyvinyl alcohol to achieve excellent neutron shielding properties.

The increasing utilization of nuclear energy and radiation medicine has urged flexible neutron shielding materials for personal protection. However, it was a challenge to manufacture neutron shielding materials with good flexibility and efficient neutron shielding performance. Herein, a new type of hybrid filler named Gd@MXene nanoflakes were successfully synthesized via one step-hydrothermal reaction and used for efficient neutron shielding, which was composed of two-dimensional (2D) Ti3C2Tx-MXene nanoflakes and zero-dimensional Gd nanoparticles (NPs). Inspired by fish scales, the spin coating method was employed to manufacture the film composed of polyvinyl alcohol (PVA) and Gd@MXene, which aligned random Gd@MXene into oriented 2D fish scale-like barrier walls. The 2D fish scale-like Gd@MXene barrier walls scattered the neutron rays multiple times between the nanoflakes, thereby improving the neutron absorption efficiency of Gd atoms. The film showed excellent neutron shielding performance and thermal conductivity; the neutron shielding rate of 20-Gd@MXene/PVA with a thickness of 62 µm was 3.36 times higher than that of pure PVA. The thermal conductivity of Gd@MXene/PVA was nearly 10 times higher than that of pure PVA. This work introduced a novel film for neutron radiation shielding and had potential applications in personal wearable protective equipment.

A Machine Learning-Modified Novel Nomogram to Predict Perioperative Blood Transfusion of Total Gastrectomy for Gastric Cancer.

Background: Perioperative blood transfusion reserves are limited, and the outcome of blood transfusion remains unclear. Therefore, it is important to prepare plans for perioperative blood transfusions. This study aimed to establish a risk assessment model to guide clinical patient management. Methods: This retrospective comparative study involving 513 patients who had total gastrectomy (TG) between January 2018 and January 2021 was conducted using propensity score matching (PSM). The influencing factors were explored by logistic regression, correlation analysis, and machine learning; then, a nomogram was established. Results: After assessment of the importance of factors through machine learning, blood loss, preoperative controlling nutritional status (CONUT), hemoglobin (Hb), and the triglyceride-glucose (TyG) index were considered as the modified transfusion-related factors. The modified model was not considered to be different from the original model in terms of performance, but is simpler. A nomogram was created, with a C-index of 0.834, and the decision curve analysis (DCA) demonstrated good clinical benefit. Conclusions: A nomogram was established and modified with machine learning, which suggests the importance of the patient's integral condition. This emphasizes that caution should be exercised regarding transfusions, and, if necessary, preoperative nutritional interventions or delayed surgery should be implemented for safety.

MiR-223 Promotes Tumor Progression via Targeting RhoB in Gastric Cancer.

Gastric cancer (GC) is among the most prevalent causes of cancer-related death globally. MiR-223 has been implicated in a variety of cellular mechanisms linked to cancer progression. However, the miR-223 expressions and its function in GC are unknown. We discovered that miR-223 expression was raised in GC tissues in comparison with nearby normal tissues in this investigation. Additionally, multiplied miR-223 expression was strongly linked with TNM stage (p=0.022), live metastasis (p=0.004),lymph node metastasis (p=0.004),and Borrmann type and was associated with an unfavorable prognostic for patients with GC. Furthermore, suppressing miR-223 significantly increased cell death and prevented cell migration and invasion in vitro. Additionally, miR-223 silencing decreased tumor development in vivo. Additionally, we discovered that miR-223 enhanced GC development by specifically targeting RhoB. In summary, our findings reveal that miR-223 increases tumor progression in GC by targeting RhoB, suggesting that it could serve to be a potential biomarker for the prediction of the disease.

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway.

Introduction: Chemoresistance is a major barrier in the treatment of colorectal cancer (CRC) and many other cancers. ENO1 has been associated with various biological characteristics of CRC. This study aimed to investigate the function of ENO1 in regulating 5-Fluorouracil (5-FU) resistance in CRC. Methods: ENO1 level in 120 pairs of tumor tissues and adjacent normal tissues was examined by immunohistochemistry, and the correlation between ENO1 expression and prognosis was explored by survival analysis. Its role and potential mechanisms in regulating 5-FU resistance in CRC were studied by Western blotting, MTT assay, colony formation assay and transwell invasion assay. Murine xenograft assay was implied to verify the results in vivo. Results: Our study indicated that ENO1 was elevated in CRC tissues and was associated with poor patient prognosis. High levels of ENO1 expression were detected as a significant influencing factor for overall survival. Furthermore, ENO1 expression was found to have increased in drug-resistant cells (HCT116/5-FU and SW620/5-FU) constructed by increasing concentrations of 5-FU. Knockdown of ENO1 markedly increased the drug susceptibility and inhibited the proliferation and migration ability of HCT116/5-FU and SW620/5-FU cells. It was found that down-regulation of ENO1 inhibited the epithelial-mesenchymal transformation (EMT) signaling process. Finally, a murine xenograft assay verified that the depletion of ENO1 alleviated 5-FU resistance. Conclusion: This study identified that ENO1 regulated 5-FU resistance via the EMT pathway and may be a novel target in the prevention and treatment of 5-FUresistant CRC.

Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway.

BACKGROUND: Different methods for digestive tract reconstruction have a complex impact on the nutritional status of gastric cancer (GC) patients after radical gastrectomy. Previous studies reported that Roux-en-Y (R-Y) reconstruction resulted in obvious weight reduction and improvement in type 2 diabetes in obese patients. We investigated the relationship between R-Y reconstruction, gut microbiota, and the NLRP3 inflammasome in GC patients with poor basic nutrition. METHODS: Changes in the gut microbiota after radical gastrectomy accomplished by different methods of digestive tract reconstruction were investigated via fecal microbiota transplantation. The underlying mechanisms were also explored by analyzing the role of the microbiota, butyrate, and the NLRP3 inflammasome in the colon tissues of colitis model mice and GC patients after radical gastrectomy. FINDINGS: R-Y reconstruction effectively relieved intestinal inflammation and facilitated nutrient absorption. 16S rRNA analysis revealed that gavage transplantation with the fecal microbiota of R-Y reconstruction patients could reverse dysbacteriosis triggered by radical gastrectomy and elevate the relative abundance of some short-chain fatty acid (SCFA)-producing bacteria. Subsequently, butyrate negatively regulated the NLRP3-mediated inflammatory signaling pathway to inhibit the activation of macrophages and the secretion of pro-inflammatory mediators such as caspase-1 and interleukin (IL)-1ß, decreasing the level of intestinal inflammation and promoting nutrient absorption. INTERPRETATION: R-Y reconstruction induced colonization with SCFA-producing bacteria to alleviate radical gastrectomy-induced colitis by down-regulating the NLRP3 signaling pathway. This can be a new strategy and theoretical basis for the management of the postoperative nutritional status of GC patients. FUNDING: This work was supported by the National Nature Science Foundation of China (81974375), the BoXi cultivation program (BXQN202130), and the Project of Youth Foundation in Science and Education of the Department of Public Health of Suzhou (KJXW2018001).