Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-ß1/Smad signaling pathway.

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 µM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell apoptosis and G0/G1 cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-ß1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating cancer cells with a TGF-ß signaling inhibitor. Lastly, the in vivo anti breast cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

Nanoengineering Natural Leather for Dynamic Thermal Management and Electromagnetic Interference Shielding.

Unpredictable and extreme weather conditions, along with increasing electromagnetic pollution, have resulted in a significant threat to human health and productivity, causing irreversible damage to society's well-being and economy. However, existing personal temperature management and electromagnetic protection materials lack adaptability to dynamic environmental changes. To address this, a unique asymmetric bilayer leather/a-MWCNTs/CA fabric is developed by vacuum-infiltrating interconnected a-MWCNTs networks into natural leather's microfiber backbone and spraying porous acetic acid (CA) on the reverse side. Such fabric achieves simultaneous passive radiation cooling, heating, and anti-electromagnetic interference functions without external energy input. The fabric's cooling layer has high solar reflectance (92.0%) and high infrared emissivity (90.2%), providing an average subambient radiation cooling effect of 10 °C, while the heating layer has high solar absorption (98.0%), enabling excellent passive radiative heating and effective compensation for warming via Joule heating. Additionally, the fabric's 3D conductive a-MWCNTs network provides electromagnetic interference shielding effectiveness of 35.0 dB mainly through electromagnetic wave absorption. This multimode electromagnetic shielding fabric can switch between cooling and heating modes to adapt to dynamic cooling and heating scenarios, providing a new avenue for sustainable temperature management and electromagnetic protection applications.

Identification and characterization of immune-related microRNAs in hybrid snakehead(Channa maculata♀ × Channa argus♂)after treated by Echinacea purpurea (Linn.) Moench.

Echinacea purpurea (Linn.) Moench (EP) is a globally popular herbal medicine, which showed effects on growth promotion, antioxidant and immunomodulatory activities in fish culture world widely. However, there are few studies about the effects on miRNAs by EP in fish. The hybrid snakehead fish (Channa maculate♀ × Channa argus ♂) was new important economic specie of freshwater aquaculture in China with high market value and demand while there were only a few reports about its miRNAs. To overview immune-related miRNAs of the hybrid snakehead fish and to further understand the immune regulating mechanism of EP, we herein constructed and analyzed three small RNA libraries of immune tissues including liver, spleen and head kidney of the fish with or without EP treatment via Illumina high-throughput sequencing technology. Results showed that EP can affect the immune activities of fish by the miRNA-regulated ways. Totally, 67 (47 up and 20 down) miRNAs in liver, 138 (55 up and 83 down) miRNAs in spleen, and 251 (15 up and 236 down) miRNAs in spleen were detected, as well as 30, 60, 139 kinds of immune-related miRNAs belonging to 22, 35 and 66 families of the three tissues respectively. The expressions of 8 immune-related miRNA family members were found in all the three tissues, including miR-10, miR-133, miR-22 and etc. Some miRNAs have been identified involved in the innate and adaptive immune responses, such as the miR-125, miR-138, and miR-181 family. Ten miRNA families with antioxidant target genes were also discovered, including miR-125, miR-1306, and miR-138, etc. Results from Gene Ontology (GO) and KEGG pathway analysis further confirmed there are a majority immune response targets of the miRNAs involved in the EP treatment process. Our study deepened understanding roles of miRNAs in fish immune system and provides new ideas for the study of immune mechanism of EP.

Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM.

BACKGROUND: Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. RESULTS: The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. CONCLUSIONS: The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.

CCL21/CCR7 axis regulates demyelination and vascular cognitive impairment in a mouse model for chronic cerebral hypoperfusion.

OBJECTIVES: White matter lesions (WML) are usually accompanied by cognitive decline, which consist of axonal loss and demyelination. CC chemokine ligand 21 (CCL21) and its receptor C-C chemokine receptor 7 (CCR7) belong to the chemokine family, which are involved in many diseases. However, their function in the central nervous system (CNS) is still unexplored. This study aimed to explore the role of CCL21/CCR7 axis in the pathological process of chronic ischemia-induced WML. METHODS: Bilateral common carotid artery stenosis (BCAS) was employed in C57BL/6 mice as the in vivo WML model. Microarray analysis was performed to detect the overall molecular changes induced in the endothelial cells by BCAS. Q-PCR, Western blotting, and immunofluorescence staining were performed to evaluate expression levels of the related molecules. The mice were injected with LV-CCL21-GFP virus in the corpus callosum to overexpress CCL21. WML degree was determined via MRI, and cognitive ability was assessed by Y-maze and novel object recognition tests. Myelin sheath integrity was evaluated via immunofluorescence staining. RESULTS: CCL21 was significantly downregulated in endothelial cells after BCAS and CCL21 overexpression alleviated BCAS-induced cognitive deficits and demyelination. Furthermore, CCR7 was found to be mainly expressed in oligodendrocytes (OLs) after exposed to hypoxia and CCR7 silencing blocked the protective effects induced by CCL21 overexpression. Conclusions CCL21/CCR7 axis may play a key role in demyelination induced by BCAS. This might provide a novel therapeutic target for WML.

The Impact of Firm's Unethical Behavior in Investment Decisions Among Young Investors in China.

Purpose: There is ample evidence that investors respond negatively to firm's unethical behavior. However, researchers cannot explain investors' reactions and the mechanisms of change when faced with firm's unethical behavior. By collecting and analyzing data from questionnaires, this study investigated the effects of firm's unethical behavior on investors' willingness to invest and further focused on different targets involved in unethical events. Moreover, this study explored the roles of firm development stages and the moderation effect of investors' moral support level. It aims to reveal investors' decisions on firm's unethical behaviors in different situations. Methods: This study employed a 2 (behavioral ethics: unethical behavior versus normal behavior) X 2 (stages of firm development: startups versus mature firms) X 4 (targets involved in the events: employees, peers, customers, and society) mixed design. Two hundred and fifty-seven participants were finally recruited for final analysis, and then repeated-measures ANOVAs were adopted to assess the valid data collected from 257 participants. Results: The results showed that disclosure of unethical behavior in due diligence reports significantly decreased investors' willingness to invest. However, investor willingness was higher for startups with unethical behavior than for unethical mature firms. Investors' willingness to invest decreased most significantly when evaluating firms with unethical behavior toward employees, followed by society and peers. Their willingness to invest decreased the least when evaluating firms exhibiting unethical behavior toward customers. The level of investors' moral support moderated the above effects, that is, the higher the moral support, the more considerable the decrease in investment willingness in unethical firms. Conclusion: Current results demonstrated that when facing firms with unethical behaviors, investors would make investment decisions after considering the firm's stage of development and the stakeholder of the unethical event. This study provides a valuable theoretical basis for decision-making by government, institutional investors, and firm managers.

Cerebral small vessel disease combined with cerebral collaterals to predict the prognosis of patients with acute large artery atherosclerotic stroke.

Background and purpose: Besides cerebral collaterals, few studies have examined other additional factors affecting the prognosis of patients with large artery atherosclerotic (LAA) stroke. Our study aims to explore the effect of the cerebral small vessel disease (SVD) and the effects of its interaction with cerebral collaterals on the prognosis of patients with acute LAA stroke. Method: Patients aged 18 years or older with LAA stroke within 24 h after stroke onset were consecutively enrolled. The functional outcome was determined using the modified Rankin Scale (mRS) at 3 months after stroke onset. Logistic multivariate analyses were used to identify the risk factors for stroke prognosis. Receiver operating characteristic (ROC) curves were constructed to compare the effects of cerebral collaterals and SVD on predicting the prognosis. Results: Of the 274 enrolled patients, 174 (63.50%) were identified as having a favorable prognosis, and 100 (36.50%) were identified as having an unfavorable prognosis. After adjusting for covariates, the logistic regression analysis identified that unfavorable prognosis was related to the total SVD score (Model 1, adjusted odds ratio = 1.73, 95% CI: 1.15-2.61, P < 0.01; Model 2, adjusted odds ratio = 1.85, 95% CI: 1.23-2.79, P < 0.01) and Tan score (Model 1, adjusted odds ratio = 0.38, 95% CI: 0.23-0.64, P < 0.01; Model 2, adjusted odds ratio = 0.52, 95% CI: 0.33-0.82, P < 0.01). Compared with cerebral collaterals (AUC = 0.59; 95% CI: 0.52-0.67; P < 0.01) or SVD (AUC = 0.62; 95% CI: 0.56-0.69; P < 0.01) alone, the combination of collaterals and SVD (AUC = 0.66; 95% CI: 0.59-0.73; P < 0.01) had higher diagnostic value for an unfavorable prognosis, and the optimal sensitivity and specificity were 77.01 and 53.00%, respectively. Conclusions: The total SVD burden was related to the prognosis of patients with LAA stroke. Compared with cerebral collaterals or SVD alone, cerebral collaterals combined with total SVD burden are better at predicting the prognosis of patients with acute LAA stroke.

Vitamin E performs antioxidant effect via PAP retrograde signaling pathway in Nile tilapia (Oreochromis niloticus).

PAP (3'-phosphoadenosine 5'-phosphate) is a ubiquitous phosphoric acid and a natural inhibitor of the XRN (5'-3'exoribonuclease) family. It was proved to enter the nucleus through the retrograde signaling pathway and inhibit XRN2 to prevent the degradation of miRNA precursors, thus promoting the anti-oxidation miRNA level in Arabidopsis thaliana. Vitamin E (tocopherol) was proved to promote the accumulation of PAP in the plant, which facilitates PAP into the nucleus to accomplish its antioxidant function. However, the relationship between VE and PAP in animals is unclear. To identify the relationship between VE and PAP and to uncover the function of PAP in fish, we investigated the performance of VE and PAP in Nile tilapia by comparing the antioxidant indicators (SOD, GSH-Px, and CAT), the Keap1-Nrf2 signaling pathway, and the miRNA expression profiles. Results showed that the antioxidant effect of VE and PAP showed similar character either in tilapia liver or in serum: the activities of GSH-Px and CAT of both groups were significantly increased (P < 0.05); the SOD activity of the VE group was significantly increased (P < 0.05), and although the result of the PAP group was not so significant (P > 0.05), PAP improved the SOD level, too. The two groups also showed similar character in the tilapia liver; both did not significantly increase the liver δ-VE content (P > 0.05). However, VE significantly increased the content of α-VE and γ-VE (P < 0.05), while the PAP group was insignificant (P > 0.05). Feed with VE and intraperitoneal injection of PAPs reagent both increased the PAP content in the liver of tilapia, and the effect of the VE group was more significant (P < 0.05) than that of the PAP group (P > 0.05). Both groups reduced the expression of Keap1 and Cullin3 genes and improved the level of HO-1 gene expression, with the improved miRNA level of Nrf2. As a logical result, they decreased the expression of XRN1 and XRN2. By profile sequencing, we further identified some antioxidant closely related miRNAs shared in the VE and PAP groups, including miR-30, miR-24, miR-19b, and miR-100. By comparing the regulating mechanism of VE and PAP of feed supply and intraperitoneal injection, we proved that VE and PAP were closely related in fish; VE promoted the gathering of PAP. The latter retrograded into the nucleus of the fish liver to inhibit the expression of XRN genes and to up-regulate antioxidant miRNA levels as it does in plants. Only the PAP can accomplish the antioxidant activities, while VE promotes the process. Our study laid the foundation for the application of PAP as a new antioxidant agent in fish farming and benefit a further understanding of the VE antioxidant function in fish.

The Impact of the Scale of Third-Party Logistics Guaranteeing Firms on Bank Credit Willingness in Supply Chain Finance: An ERP Study.

Supply chain financing guaranteed by third-party logistics (3PL) firms is an effective way to solve the financing difficulties of small and medium-sized enterprises (SMEs). Studies have explored factors that affect the willingness of supply chain financial credit providers under guarantee of 3PL firms (e.g., the scale of financing enterprises and credit). However, whether the scale of 3PL firms will affect the bank's credit decision has not been studied, as well as the neural processing of credit decisions. To clarify these issues, this study extracted behavioral and event-related potentials (ERPs) data when participants performed a selection task of judging whether to grant credit to guaranteed financing-seeking enterprises according to the large or small scale of the 3PL guaranteeing firms. The behavioral results showed that under the condition of a large-scale 3PL guaranteeing firm, the willingness to provide credit to SMEs was higher than that under the condition of a small-scale 3PL guaranteeing firm. This finding indicates there was credit scale discrimination against 3PL guaranteeing firms in supply chain finance. The ERP results showed that compared with the condition of a large-scale 3PL guaranteeing firm, a greater N2 amplitude was induced under the condition of a small-scale 3PL guaranteeing firm, which indicated that credit decision makers experienced greater perceived risk and more decision-making conflict. In contrast, a larger LPP amplitude was detected under the condition of a large-scale 3PL guaranteeing firm (as opposed to a small-scale firm), which indicated that large-scale 3PL guaranteeing firms received more positive comments and more positive emotions from credit decision makers than small-scale 3PL guaranteeing firms. Based on these results, this study reveals the cognition process of credit decision makers regarding the impact of the 3PL guaranteeing firm scale on the willingness to provide credit in supply chain finance and explains the theory of credit scale discrimination from the perspective of decision neuroscience.

New Schemes for Investment in of Small and Medium-Sized Enterprises of China: Role of Access to Finance, Innovation, and Sustainability.

Firm innovation relies heavily on financing, which is why it is a hot topic in the fields of finance and innovation management. Organizations can make strategic investments in production factors to develop competitive advantages because they have access to financial resources. This study investigated how financial literacy, innovativeness, and environmental sustainability influence the sustainability of small and medium-sized enterprises (SMEs). This was set as the primary objective in order to better understand the nature of the impact of financial literacy and innovation on the sustainability of SME firms. To test the hypotheses, structural equation modeling (SEM) was applied using data collected from 300 small businesses firms in China. The results revealed that financial literacy and innovativeness significantly influence small firms' sustainability. Additionally, social inclusion significantly affects small firms' sustainability, and sequentially has a significant effect on their performance. Research findings suggested that small businesses incorporate sustainability models into their operations and enhance financial knowledge in order to maintain sustainability.

Nitro-oleic acid-mediated blood-brain barrier protection reduces ischemic brain injury.

Nitro-oleic acid (OA-NO2), a nitroalkene formed in nitric oxide-dependent oxidative reactions, has been found in human plasma and is thought to regulate pathophysiological functions. Recently, accumulating evidence suggests that OA-NO2 may function as an anti-inflammatory mediator, and ameliorate the progression of diabetes and cardiovascular diseases. However, the role of OA-NO2 in ischemic brain injury remains unexplored. In this study, C57BL/6 mice were subjected to 1 h transient middle cerebral artery occlusion (MCAO) and followed by 1- 7 days of reperfusion. These mice were treated with vehicle, OA, or OA-NO2 (10 mg/kg) via tail vein injection at 2 h after the onset of MCAO. Our results show that intravenous administration of OA-NO2 led to reduced BBB leakage in ischemic brains, reduced brain infarct, and improved sensorimotor functions in response to ischemic insults when compared to OA and vehicle controls. Also, OA-NO2 significantly reduced BBB leakage-triggered infiltration of neutrophils and macrophages in the ischemic brains. Moreover, OA-NO2 treatment reduced the M1-type microglia and increased M2-type microglia. Mechanistically, OA-NO2 alleviated the decline of mRNA and protein level of major endothelial TJs including ZO-1 in stroke mice. Treatment of OA-NO2 also significantly inhibited stroke-induced inflammatory mediators, iNOS, E-selectin, P-selectin, and ICAM1, in mouse brains. In conclusion, OA-NO2 preserves BBB integrity and confers neurovascular protection in ischemic brain damage. OA-NO2-mediated brain protection may help us to develop a novel therapeutic strategy for the treatment of ischemic stroke.

MicroRNAs and Related Cytokine Factors Quickly Respond in the Immune Response of Channel Catfish to Lipopolysaccharides and ß-Glucan Stimulation.

MicroRNAs (miRNAs) are well-known as powerful regulators of gene expression, with their potential to serve for immunology widely researched in mammals and birds but rarely in fishes. To better understand fish immunology behavior, we herein investigated nine immune-related miRNAs that were reported in other animals, as well as five related cytokine factors and lysozyme (LZM) in the liver, anterior kidney, and spleen of Channel Catfish Ictalurus punctatus after being stimulated by lipopolysaccharides (LPS) and ß-glucan. We also predicated the potential targets of these miRNAs via bioinformatics and further investigated nine of them via quantitative real-time PCR. Results showed that expressions of the nine miRNAs were quickly changed in varying extent after stimulation by LPS, especially for miR-122, miR-142a, miR-155, and miR-223, which were significantly changed in spleen, and the same occurred for the LZM and three cytokine factors TNF-α, IFN-γ and TLR2. Compared with LPS, although most of the miRNAs and the cytokine genes were also affected by ß-glucan, the extent of the effect was weak. Bioinformatics analysis revealed many immune-related targets of the miRNAs, with some of them reported by previous studies. For the nine investigated target genes, seven targets (77.8%) were significantly upregulated after the stimulation of LPS. It therefore can be inferred that the immune-related miRNAs, LZM, and cytokine factors elicited quick immune responses of Channel Catfish to LPS stimulation as in other animals, but the regulation mechanism of miRNAs might be complex and diverse. This research will contribute to a better understanding will support further immunology research in fishes.

Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.

BACKGROUND AND AIMS: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. RESULTS: The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. CONCLUSION: Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

L-fucose ameliorates the carcinogenic properties of Fusobacterium nucleatum in colorectal cancer.

Fusobacterium nucleatum (Fn) is considered a promoting factor in colorectal cancer (CRC); however, only a few studies have investigated therapies against Fn. L-fucose is a natural monosaccharide that has prebiotic potential. The present study aimed to investigate the effect of L-fucose on the carcinogenic properties of Fn. The HCT116 and SW480 colon cancer cell lines were treated with Fn and Fn+L-fucose (Fnf), respectively. The Cell Counting Kit-8 (CCK-8), colony formation, Transwell migration and invasion and wound healing assays were performed to assess the proliferative, migratory and invasive abilities of the cells, respectively. Western blot was performed to detect the protein levels of jak/stat3 pathway components and EMT. The results of the CCK-8, colony formation, Transwell and wound healing assays demonstrated that treatment with Fn significantly enhanced the proliferative, migratory and invasive abilities of HCT116 and SW480 colon cancer cells. Notably, these effects were significantly reversed following addition of L-fucose. Furthermore, L-fucose inhibited the carcinogenic properties of Fn to activate the stat3 pathway and epithelial-to-mesenchymal transition. Taken together, the results of the present study suggest that L-fucose ameliorates the carcinogenic properties of Fn in vitro, and thus may serve as a novel therapeutic target for flora-related colon cancer.

Predictors of pain response after endoscopic ultrasound-guided celiac plexus neurolysis for abdominal pain caused by pancreatic malignancy.

BACKGROUND: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) has gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. However, response to treatment is variable. AIM: To identify the efficacy of EUS-CPN and explore determinants of pain response in EUS-CPN for pancreatic cancer-associated pain. METHODS: A retrospective study of 58 patients with abdominal pain due to inoperable pancreatic cancer who underwent EUS-CPN were included. The efficacy for palliation of pain was evaluated based on the visual analog scale pain score at 1 wk and 4 wk after EUS-CPN. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response. RESULTS: A good pain response was obtained in 74.1% and 67.2% of patients at 1 wk and 4 wk, respectively. Tumors located in the body/tail of the pancreas and patients receiving bilateral treatment were weakly associated with a good outcome. Multivariate analysis revealed patients with invisible ganglia and metastatic disease were significant factors for a negative response to EUS-CPN at 1 wk and 4 wk, respectively, particularly for invasion of the celiac plexus (odds ratio (OR) = 13.20, P = 0.003 for 1 wk and OR = 15.11, P = 0.001 for 4 wk). No severe adverse events were reported. CONCLUSION: EUS-CPN is a safe and effective form of treatment for intractable pancreatic cancer-associated pain. Invisible ganglia, distant metastasis, and invasion of the celiac plexus were predictors of less effective response in EUS-CPN for pancreatic cancer-related pain. For these patients, efficacy warrants attention.

Rectal mucosal prolapse with an emphasis on endoscopic ultrasound appearance.

AIM: The diagnosis of mucosal prolapse syndrome (MPS) continues to be a challenge. Endoscopic ultrasound (EUS) is of clinical value in anorectal diseases. This study seeks to investigate the use of EUS in the diagnosis of MPS. METHODS: A total of 39 patients diagnosed with MPS between June 2015 to December 2019 were included in this study. Their clinical histories, endoscopic images, EUS images, and pathological data were retrospectively collected, and the EUS images were reviewed to summarize the characteristics of MPS. RESULTS: In total, 39 MPS patients were enrolled. The main presenting symptoms were bleeding (61.5%) and constipation (53.8%). Gross appearance of the rectal lesions was mainly classified into three types: 51.3% of the lesions were polypoidal/nodular, 33.3% were ulcerative and 15.4% were flat with erythematous mucosa only. A total of 10 patients underwent EUS operation. With regard to the EUS appearance of MPS, four patients with polypoidal/nodular lesions showed thickening of the mucosa on EUS. The diffuse thickening of the mucosa-submucosa layer and disappearance of the architectural structure was observed in four patients with ulcerative lesions. Finally, the thickening of the muscularis propria was observed in two flat lesions. The serosal layers were intact in all the MPS patients. Neither blood flow signals nor regional lymph nodes were observed on EUS. CONCLUSION: The EUS characteristics for MPS corresponding to different gross appearance can be classified into three types. These findings suggest that EUS is useful in the diagnosis of MPS.

Bioinformatics analysis of immune infiltration in glioblastoma multiforme based on data using a methylation chip in the GEO database.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive and malignant tumor of the central nervous system. The study was to obtain the data of immune cell infiltration based on the data of a methylation chip in the GEO, and to clarify its prognostic significance for GBM. METHODS: The methylation data of glioblastoma was obtained by using the Illumina human methylation 450k BeadChip. The corrected expression was obtained by using edge R. Limma was used to correct the expression amount of the samples, and EpiDISH was used to translate the methylation expression data, so that the expression amount was transformed into the expression matrix of immune cells. The immune cells were then co-expressed, and the proportion and correlation of related immune cells was determined. The results of the cells in each of two groups were analyzed by enrichment and PCA mapping to establish the relevant differences. RESULTS: The data of GBM patients were obtained from the methylation chip of the GEO database. Patients were divided into a long-term (SNU-LTS) (21 cases), and short-term survival group (SNU-STS) (12 cases). There were 73 genes with significant individual differences between the two groups (P<0.05). EpiDISH was used to translate the methylation expression data into the expression matrix of immune cells, which showed that the highest proportion of cells in groups were mono cells, while Gran cells and CD8T appeared in a very small number of samples. The positive correlation between mono and B cells was the strongest, while the negative correlation between mono and Gran cells was the strongest. A violin chart shows that there was no significant difference in the infiltration degree of six kinds of immune cells between the two groups. Principal component analysis (PCA) showed that there was individual difference between the two groups, but the overall consistency was high. CONCLUSIONS: Data on tumor immune cell infiltration can be obtained by using a methylation chip in the GEO database. This not only extends the application abilities of methylation chips but provides obvious individual differences. The study of tumor immune infiltrating cells may pave the way for targeted therapy in the treatment of GBM.

How Useful Is Endoscopic Ultrasound in Differentiating T3/T4a T Stage of Colorectal Cancer: A Prospective Study.

OBJECTIVE: Endoscopic ultrasound (EUS) is an established method for staging of colorectal cancer. Nevertheless, prior assessments of its T stage accuracy have been limited, particularly ambiguity in assessed T3 and T4a stage. This study was to characterize the EUS image features and pay attention to distinguish T3 from T4a T stage. METHODS: A total of 638 patients who prospectively underwent colorectal EUS were recorded. The final diagnoses were compared with the concurrent or follow-up histopathology. Univariate and multivariate logistic regressions were used to assess variation in diagnostic performance with case attributes. RESULTS: The accuracies of EUS in classifying colorectal cancer for overall, T1, T2, T3, and T4a stages are 73.04, 62.32, 67.46, 71.26, and 83.52%, respectively. With attention to EUS image features, the lesion penetrates the entire wall and locates below the seminal vesicles or cervix is T3 stage. If the lesion locates above clearly-defined space between the anterior rectal wall and the posterior surface of the seminal vesicles or cervix, we identify as T4a stage; However, when located above seminal vesicles or cervix but on the posterior wall of the rectum, the lesion still considers as T3 stage. The tumor location and histological type are associated with inaccuracy T stage. CONCLUSIONS: EUS provides reliable diagnostic accuracy in the colorectal cancer stage. The seminal vesicles and cervix are the important markers to predict infiltration depth for T3/T4a stage. Furthermore, the tumor location, histological type, and EUS image features for each tumor T stage should warrant attention.

Lactobacillus rhamnosus attenuates intestinal inflammation induced by Fusobacterium nucleatum infection by restoring the autophagic flux.

Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus (L. rhamnosus) on Fusobacterium nucleatum (F. nucleatum)­induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)­induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP­mCherry­LC3 construct and also by transmission electron microscopy. Autophagy­associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro­inflammatory cytokines in Caco­2 cells and aggravated DSS­induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum. L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro­inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy­related gene 16 like 1 (Atg16L1) in Caco­2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus. Finally, the PI3K/AKT/mTOR pathway was found to be involved in this process. On the whole, the present study demonstrates that the mediation of autophagy by L. rhamnosus may be involved in the protective effects against F. nucleatum­related intestinal inflammation. Thus, L. rhamnosus treatment may prove to be a novel therapeutic strategy for F. nucleatum­realated gut disorders.