LINC00942 inhibits ferroptosis and induces the immunosuppression of regulatory T cells by recruiting IGF2BP3/SLC7A11 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a high recurrence rate and a poor prognosis. Long intergenic nonprotein coding RNA 942 (LINC00942) is reported to be related to ferroptosis and the immune response in HCC and serves as an oncogene in various cancers. This research aimed to explore the contribution of LINC00942 in HCC progression. Functional assays were used to evaluate the functional role of LINC00942 in vitro and in vivo. Mechanistic assays were conducted to assess the association of LINC00942 with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) and solute carrier family 7 member 11 (SLC7A11) and the regulatory pattern of LINC00942 in HCC cells. LINC00942 was found to exhibit upregulation in HCC tissue and cells. LINC00942 facilitated HCC cell proliferation, suppressed ferroptosis, and converted naive CD4+ T cells to inducible Treg (iTreg) cells by regulating SLC7A11. Furthermore, SLC7A11 expression was positively modulated by LINC00942 in HCC cells. IGF2BP3 was a shared RNA-binding protein (RBP) for LINC00942 and SLC7A11. The binding between the SLC7A11 3' untranslated region and IGF2BP3 was verified, and LINC00942 was found to recruit IGF2BP3 to promote SLC7A11 mRNA stability in an m6A-dependent manner. Moreover, mouse tumor growth and proliferation were inhibited, and the number of FOXP3+CD25+ T cells was increased, while ferroptosis was enhanced after LINC00942 knockdown in vivo. LINC00942 suppresses ferroptosis and induces Treg immunosuppression in HCC by recruiting IGF2BP3 to enhance SLC7A11 mRNA stability, which may provide novel therapeutic targets for HCC.

A retrospective analysis of the clinical efficacy of pancreatic duct stent implantation in the management of acute biliary pancreatitis requiring ERCP.

BACKGROUND: This study aimed to investigate the feasibility, effectiveness, and safety of pancreatic duct stenting in managing acute biliary pancreatitis (ABP) necessitating endoscopic retrograde cholangiopancreatography (ERCP). It further aimed to provide valuable insights for subsequent clinical diagnosis and treatment. METHODS: This research employs an observational retrospective case-control study design, encompassing patients with ABP who underwent ERCP at the hepatobiliary surgery department of the General Hospital of Ningxia Medical University between August 1, 2018, and December 31, 2020. A total of 229 cases were screened based on inclusion and exclusion criteria. Regardless of ABP severity, patients were categorized into the stent group (141) and the non-stent group (88). Changes in blood amylase (Amy), lipase (LIP), leukocyte count (WBC), total bilirubin (TBIL), alanine aminotransferase (ALT), hematocrit (HCT), and creatinine (CR) were compared between the two groups. Moreover, variables such as recovery time for oral feeding, hospitalization duration, hospitalization costs, local complications, systemic complications, and new organ failure were recorded to assess the therapeutic effect of pancreatic duct stenting. RESULTS: No significant differences were observed in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ABP severity grade, organ failure (OF), cholangitis, or biliary obstruction between the pancreatic stent and non-stent groups (P > 0.05). There was no significant difference in the incidence of complications related to acute pancreatitis between the two groups (P > 0.05). The median fasting and hospitalization times of patients in the stent group were significantly shorter than those in the non-stent group (P < 0.05). No significant differences between the groups were observed in hospitalization costs and in-hospital mortality (P > 0.05). There were no significant variations in white blood cell (WBC) count, TBIL, ALT, and creatinine (Cr) at admission, 72 h, and in the differences between the two groups (P > 0.05). The levels of Amy at admission and 72 h in the stent group were significantly higher than those in the non-stent group (P < 0.05). The differences in LIP and HCT in the stent group were considerably higher than in the non-stent group (P < 0.05). Although no significant differences were observed in mean Amy and LIP between the two groups (P > 0.05), the mean 72-h HCT in the stent group was 38.39% (95% confidence interval [CI] 37.82%-38.96%) was lower than that in the non-stent group (39.44%, 95% CI 38.70-40.17%) (P < 0.05). CONCLUSION: In the stent group, feeding time and hospital stay were significantly shorter than those in the non-stent group. No significant differences were observed between the two groups in the incidence of complications and mortality. The HCT value decreased more rapidly in the stent group. Early pancreatic stent implantation demonstrated the potential to shorten the eating and hospitalization duration of patients with ABP, facilitating their prompt recovery. TRIAL REGISTRATION: This study was registered as a single-center, retrospective case series (ChiCTR1800019734) at chictr.org.cn.

PABPC1 promotes cell proliferation and metastasis in pancreatic adenocarcinoma by regulating COL12A1 expression.

BACKGROUND: The expression of cytoplasmic poly (A) binding protein-1 (PABPC1) has been reported in multiple cancer types. This protein is known to modulate cancer progression. However, the effects of PABPC1 expression in pancreatic adenocarcinoma (PAAD) have not been investigated. Here, we investigate the regulatory targets and molecular mechanisms of PABPC1 in PAAD. METHODS: PABPC1 and collagen type XII α1 chain (COL12A1) expression in PAAD and their role in tumor prognosis and tumor stage were investigated using The Cancer Genome Atlas database analysis. After silencing PABPC1, messenger RNA sequencing and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression of differentially expressed genes (DEGs), cell viability, apoptosis, and cell migration and invasion were explored using reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry assay, and transwell assay, respectively. The relationship between PABPC1 and COL12A1 expression was assessed by Pearson's correlation analysis. The regulatory function of COL12A1 in PABPC1-affected BXPC3 cell behavior was studied after COL12A1 was overexpressed. RESULTS: PABPC1 and COL12A1 expression was upregulated in patients with PAAD and was linked to poor prognosis. Four hundred and seventy-four DEGs were observed in BXPC3 cells after PABPC1 silencing. GO and KEGG analyses revealed that the top 10 DEGs were enriched in cell adhesion pathways. Additionally, PABPC1 silencing inhibited cell viability, migration, and invasion and accelerated apoptosis in BXPC3 cells. PABPC1 silencing increased AZGP1 and ARHGAP30 expression and decreased CAV1 and COL12A1 expression in BXPC3 cells. PABPC1 positively mediated COL12A1 expression, whereas PABPC1 knockdown induced the inhibition of BXPC3 cell proliferation, migration, and invasion. CONCLUSION: The results of this study indicate that PABPC1 may function as a tumor promoter in PAAD, accelerating BXPC3 cell proliferation and metastasis by regulating COL12A1 expression.

Femtosecond Laser-Driven Phase Engineering of WS2 for Nano-Periodic Phase Patterning and Sub-ppm Ammonia Gas Sensing.

Laser-driven phase transition of 2D transition metal dichalcogenides has attracted much attention due to its high flexibility and rapidity. However, there are some limitations during the laser irradiation process, especially the unsatisfied surface ablation, the inability of nanoscale phase patterning, and the unexploited physical properties of new phase. In this work, the well-controlled femtosecond (fs) laser-driven transformation from the metallic 2M-WS2 to the semiconducting 2H-WS2 is reported, which is confirmed to be a single-crystal to single-crystal transition without layer thinning or obvious ablation. Moreover, a highly ordered 2H/2M nano-periodic phase transition with a resolution of ≈435 nm is achieved, breaking through the existing size bottleneck of laser-driven phase transition, which is attributed to the selective deposition of plasmon energy induced by fs laser. It is also demonstrated that the achieved 2H-WS2 after laser irradiation contains rich sulfur vacancies, which exhibits highly competitive ammonia gas sensing performance, with a detection limit below 0.1 ppm and a fast response/recovery time of 43/67 s at room temperature. This study provides a new strategy for the preparation of the phase-selective transition homojunction and high-performance applications in electronics.

Direct Laser Irradiation and Modification of 2D Te for Development of Volatile Memristor.

Laser irradiation, as a kind of post-fabrication method for two-dimensional (2D) materials, is a promising way to tune the properties of materials and the performance of corresponding nano-devices. As the memristor has been regarded as an excellent candidate for in-memory devices in next-generation computing system, the application of laser irradiation in developing excellent memristor based on 2D materials should be explored deeply. Here, tellurene (Te) flakes are exposed to a 532 nm laser in the air atmosphere to investigate the evolutions of the surface morphology and atom structures under different irradiation parameters. Laser is capable of thinning the flakes, inducing amorphous structures, oxides and defects, and forming nanostructures by controlling the irradiation power and time. Furthermore, the laser-induced oxides and defects promote the migration of metal ions in Te, resulting in the formation of the conductive filaments, which provides the switching behavers of volatile memristor, opening a route to the development of next-generation nano-devices.

Nonalcoholic Fatty Liver Hepatocyte-Derived lncRNA MALAT1 Aggravates Pancreatic Cell Inflammation via the Inhibition of Autophagy by Upregulating YAP.

Background: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders, which causes death with a high mortality rate of about 30%. The study aims to identify whether the nonalcoholic fatty liver disease (NAFLD)-derived lncRNA MALAT1 participates in the inflammation of pancreatic cell and its potential mechanism. Methods: The NAFLD cell model was constructed by treating HepG2 cells with FFA. The in vitro model of acute pancreatitis (AP) was established by the administration of caerulein on AR42J cells. MALAT1 and si-MALAT1 were transfected into pancreatic cells, and then exosomes were collected from the NAFLD cell model and then were cocultured with AR42J cells. Transmission electron microscopy was used to observe the morphology of exosomes. Oil Red O staining was applied to reveal the lipid deposition. The triglyceride, IL-6, and TNF-α levels were detected using ELISA. The MALAT1 level in exosomes was detected by qRT-PCR. The CD9, CD63, CD81, and CYP2E1, LC3II, and LC3I levels were detected by western blot. Results: MALAT1 was upregulated in NAFLD-derived exosomes and increased the levels of IL-6 and TNF-α in pancreatic cells. NAFLD-derived exosomes inhibited YAP phosphorylation, decreased the levels of IL-6 and TNF-α, and reduced the ratio of LC3II/LC3I protein in pancreatic cells. Silencing MALAT1 significantly returned the inhibitory effect of NAFLD on hippo-YAP pathway. YAP1 signal transduction inhibitor CA3 reversed the decrease of LC3II/LC3I expression and the increase of IL-6 and TNF-α levels induced by MALAT1 in the AP cell model. Conclusions: NAFLD-derived MALAT1 exacerbates pancreatic cell inflammation via inhibiting autophagy by upregulating YAP.

Stenting of the pancreatic duct in the early phase of acute pancreatitis: a retrospective study.

BACKGROUND: The effectiveness of pancreatic duct (PD) stenting in the early stages of acute pancreatitis (AP) remains controversial. This study aimed to investigate the efficacy and safety of PD stenting in the early stages of AP. METHODS: This is a retrospective cohort study. The clinical data of 131 patients with AP from 2018 to 2019 were analysed and divided into two groups: the study group (n = 46, PD stenting) and the control group (n = 85, standard treatment). RESULTS: There was a statistically significant reduction in pain relief, oral refeeding, hospitalization, and intensive care unit (ICU) stay in the study group compared with that of the control group (P < 0.05). There were no significant differences in the incidence of complications between the two groups. Further multivariate analysis of risk factors for new-onset organ failure showed that the control group (odds ratio [OR] (95% confidence interval [CI]): 6.533 (1.104-70.181)) and a higher level of haematocrit (HCT) at admission (HCT > 46.1%, OR (95%CI): 8.728 (1.264-116.767)) were independent risk factors. CONCLUSIONS: In the early phase of AP, PD stenting has the potential to reduce pain relief time, oral refeeding time, ICU stay time, and overall hospital stay time. This finding highlights a new route for the treatment of AP.

Tunable Electronic Properties of Few-Layer Tellurene under In-Plane and Out-of-Plane Uniaxial Strain.

Strain engineering is a promising and fascinating approach to tailoring the electrical and optical properties of 2D materials, which is of great importance for fabricating excellent nano-devices. Although previous theoretical works have proved that the monolayer tellurene has desirable mechanical properties with the capability of withstanding large deformation and the tunable band gap and mobility conductance induced by in-plane strain, the effects of in-plane and out-of-plane strains on the properties of few-layer tellurene in different phases should be explored deeply. In this paper, calculations based on first-principles density functional theory were performed to predict the variation in crystal structures and electronic properties of few-layer tellurene, including the α and ß phases. The analyses of mechanical properties show that few-layer α-Te can be more easily deformed in the armchair direction than ß-Te owing to its lower Young's modulus and Poisson's ratio. The α-Te can be converted to ß-Te by in-plane compressive strain. The variations in band structures indicate that the uniaxial strain can tune the band structures and even induce the semiconductor-to-metal transition in both few-layer α-Te and ß-Te. Moreover, the compressive strain in the zigzag direction is the most feasible scheme due to the lower transition strain. In addition, few-layer ß-Te is more easily converted to metal especially for the thicker flakes considering its smaller band gap. Hence, the strain-induced tunable electronic properties and semiconductor-to-metal transition of tellurene provide a theoretical foundation for fabricating metal-semiconductor junctions and corresponding nano-devices.

A Cell Cycle Progression-Derived Gene Signature to Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma.

OBJECTIVE: Dysregulation of cell cycle progression (CCP) is one of the hallmarks of cancer. Here, our study is aimed at developing a CCP-derived gene signature for predicting high-risk population of hepatocellular carcinoma (HCC). METHODS: Our study retrospectively analyzed the transcriptome profiling and clinical information of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects. Uni- and multivariate cox regression models were conducted for identifying which hallmarks of cancer were risk factors of HCC. CCP-derived gene signature was developed with LASSO method. The predictive efficacy was verified by ROC curves and subgroup analyses. A nomogram was then generated and validated by ROC, calibration, and decisive curves. Immune cell infiltration was estimated with ssGSEA method. Potential small molecular compounds were predicted via CTRP and CMap analyses. The response to chemotherapeutic agents was evaluated based on the GDSC project. RESULTS: Among hallmarks of cancer, CCP was identified as a dominant risk factor for HCC prognosis. CCP-derived gene signature displayed the favorable predictive efficacy in HCC prognosis independent of other clinicopathological parameters. A nomogram was generated for optimizing risk stratification and quantifying risk evaluation. CCP-derived signature was in relation to immune cell infiltration, HLA, and immune checkpoint expression. Combining CTRP and CMap analyses, fluvastatin was identified as a promising therapeutic agent against HCC. Furthermore, CCP-derived signature might be applied for predicting the response to doxorubicin and gemcitabine. CONCLUSION: Collectively, CCP-derived gene signature was a promising marker in prediction of survival outcomes and therapeutic responses for HCC patients.

Treatment of acute pancreatitis with early pancreatic stenting: a case series of 336 patients.

BACKGROUND: Pancreatic duct (PD) obstruction and hypertension may play a central role in the onset and progression of acute pancreatitis (AP). However, only a few studies have reported using pancreatic stenting to relieve PD obstruction in the early phase of AP, with conflicting results. Whether pancreatic stenting is effective in the early phase of AP remains unknown. We conducted this experiment in order to study the therapeutic efficacy and safety of pancreatic stenting in the early stage of AP. METHODS: We conducted a retrospective analysis of 336 AP patients from 2011 to 2018 who underwent pancreatic stenting within 48 hours of admission. RESULTS: A total of 330 (98.2%) patients underwent successful pancreatic stenting, of whom 23 (7.0%) had severe AP, 178 (53.9%) had moderately severe AP, and 129 (39.1%) had mild AP. Visible PD obstructive material was observed in 94 (28.5%) patients. The mean oral refeeding time since admission and length of hospital stay were 3.5±2.7 and 7.4±6.7 days, respectively. Procedure-related adverse events, in-hospital mortality, and local complication rates were 0.3%, 0.3%, and 7.6%, respectively. CONCLUSIONS: Early endoscopic pancreatic stenting in AP patients effectively shortened the fasting time and length of hospital stay and did not increase the risk of adverse events, death, or local complications. A further prospective randomized controlled clinical trial is currently underway to validate the safety and efficacy of this procedure.

miR­32­5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1.

Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)­32­5p in PAAD cells. miR­32­5p mimic and inhibitor were used to transfect the human PAAD AsPC­1 cell line to determine the role of miR­32­5p in cell proliferation and metastasis. The starBase database predicted the binding of miR­32­5p to the target gene TBC/LysM­associated domain containing 1 (TLDC1). Further analyses were performed to assess miR­32­5p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR­32­5p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR­32­5p and TLDC1 was verified using the dual­luciferase reporter assay. miR­32­5p and TLDC1 expression levels were detected by reverse transcription­quantitative PCR and western blotting, respectively. The Cell Counting Kit­8 assay was utilised to assess cell proliferation, whereas the wound­healing and Transwell assays were conducted to assess cell migration and invasion, respectively. miR­32­5p expression levels were markedly lower in PAAD tissue compared with those in healthy tissue, and were significantly lower in PAAD cell lines compared with those in the human pancreatic duct cell line HPDE6, which corresponded with poor prognosis. miR­32­5p significantly inhibited the proliferation of PAAD cells and markedly reduced migration and invasion compared with the negative controls. miR­32­5p was shown to target TLDC1, with miR­32­5p expression in PAAD being negatively correlated with TLDC1 expression. High TLDC1 expression levels were associated with a poorer prognosis compared with low TLDC1 expression levels. Co­transfection of miR­32­5p mimic and pcDNA/TLDC1 demonstrated that TLDC1 significantly reversed miR­32­5p­mediated inhibition of the proliferation, migration and invasion of PAAD cells. Overall, the present study demonstrated that miR­32­5p may serve as a tumor­suppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. Therefore, miR­32­5p may serve as a potential diagnostic or prognostic marker for PAAD.

Down-Regulation of C3aR/C5aR Inhibits Cell Proliferation and EMT in Hepatocellular Carcinoma.

Complement 3a (C3a) and complement 5a (C5a), small cleavage fragments generated by complement activation, has been previously shown to be obviously up-regulated in highly metastatic hepatocellular carcinoma (HCC) cells. However, their functional roles in HCC cells remains unclear. Here, we investigated the biological function of G protein-coupled receptor C3aR/C5aR using small interference RNA in HCC cells. Our data showed that C3aR and C5aR knockdown significantly inhibited the proliferation, migration and invasion of HCC cells using CCK-8, colony formation and transwell assays. Flow cytometry assay showed C3aR and C5aR knockdown induced cell cycle G0/G1 phase arrest and apoptosis in HCC cells. Moreover, we found down-regulation of C3aR/C5aR obviously down-regulated the expression of PCNA, Ki-67 and suppressed the epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin) in HCC cells. Collectively, our data demonstrated that targeting C3aR/C5aR may hold promise for the treatment of HCC.

LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis.

This study aims to detect expression level of long non-coding RNA (lncRNA) FLJ33360 in hepatocellular carcinoma (HCC) and its regulatory effects on accelerating malignant progression of HCC. Expression levels of FLJ33360 in 29 matched HCC tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After transfection of sh-FLJ33360#1 in Bel-7402 and HepG2 cells, changes in migratory and invasive capacities were evaluated by Transwell and wound healing assay. Potential miRNAs targeting FLJ33360 were verified. The correlation between expression levels of FLJ33360 and miRNA-140 in HCC tissues was determined. At last, potential influences of FLJ33360/miRNA-140 regulatory loop on HCC phenotypes were determined by rescue experiments. FLJ33360 was upregulated in HCC tissues relative to paracancerous ones. After knockdown of FLJ33360, migratory and invasive capacities in Bel-7402 and HepG2 cells were attenuated. There were five miRNA candidates predicted to bind FLJ33360, and miRNA-140 was the most differentially expressed by FLJ33360 regulation. Dual-luciferase reporter gene assay confirmed the binding between FLJ33360 and miRNA-140. Besides, their expression levels were negatively correlated in HCC tissues. Moreover, knockdown of miRNA-140 could stimulate metastatic ability in HCC. At last, rescue experiments verified the involvement of miRNA-140 in FLJ33360-regulated HCC progression. LncRNA FLJ33360 is upregulated in HCC. It accelerates the metastasis of HCC through targeting miRNA-140/MMP9 axis.

Oxaliplatin reverses the GLP-1R-mediated promotion of intrahepatic cholangiocarcinoma by altering FoxO1 signaling.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, with a 5-year survival rate of <10%; effective drug treatment for ICC is currently lacking. Glucagon-like peptide-1 receptor (GLP-1R) is upregulated in ICC; however, the functions of GLP-1R in ICC remain unknown. In this study, the upregulation of GLP-1R was confirmed in ICC cells using reverse transcription-quantitative polymerase chain reaction and western blot analysis, and GLP-1R was determined to promote the migration and invasion of ICC cells using Transwell assays. This tumor-promoting effect depended on the upregulation of epithelial-mesenchymal transformation-associated proteins, which was mediated by the FoxO1 signaling pathway. It was also indicated that following oxaliplatin treatment, the effects of GLP-1R on EMT and invasion were reversed. This functional reversion was associated with the reduced phosphorylation of S256 in forkhead box O1 (FoxO1) and an increase in the levels of unphosphorylated FoxO1. These findings suggest that incretin-based therapies may increase the risk of ICC metastasis and should not be used solely for the treatment of patients with ICC.

[Studies on phenolic compounds from Polygonum aviculane].

OBJECTIVE: To study the chemical constituents from the aerial parts of Polygomun aviculane. METHOD: The chemical constituents were isolated by silica gel column chromatography and preparative silica thin layer chromatography, and their structures were elucidated on the basis of physico-chemical evidences and spectroscopic analysis (IR, MS, 1H and 13C-NMR). RESULT: Seven phenolic compounds were identified as rosmarinic acid (1), gallic acid (2), gentisic acid 5-O-(6'-O-galloyl)-beta-D-glucopyranoside (3), caffeic acid (4), p-coumaric acid (5), ethyl caffeate (6) and acteoside (7), respectively. CONCLUSION: Compounds 1, 3, 6 and 7 were isolated from this plant for the first time. These results provided theoretical evidences for the further bioactive investigation on this plant.