The projection-specific signals that establish functionally segregated dopaminergic synapses.

Dopaminergic projections regulate various brain functions and are implicated in many neuropsychiatric disorders. There are two anatomically and functionally distinct dopaminergic projections connecting the midbrain to striatum: nigrostriatal, which controls movement, and mesolimbic, which regulates motivation. However, how these discrete dopaminergic synaptic connections are established is unknown. Through an unbiased search, we identify that two groups of antagonistic TGF-ß family members, bone morphogenetic protein (BMP)6/BMP2 and transforming growth factor (TGF)-ß2, regulate dopaminergic synapse development of nigrostriatal and mesolimbic neurons, respectively. Projection-preferential expression of their receptors contributes to specific synapse development. Downstream, Smad1 and Smad2 are specifically activated and required for dopaminergic synapse development and function in nigrostriatal vs. mesolimbic projections. Remarkably, Smad1 mutant mice show motor defects, whereas Smad2 mutant mice show lack of motivation. These results uncover the molecular logic underlying the proper establishment of functionally segregated dopaminergic synapses and may provide strategies to treat relevant, projection-specific disease symptoms by targeting specific BMPs/TGF-ß and/or Smads.

A role for axon-glial interactions and Netrin-G1 signaling in the formation of low-threshold mechanoreceptor end organs.

Low-threshold mechanoreceptors (LTMRs) and their cutaneous end organs convert light mechanical forces acting on the skin into electrical signals that propagate to the central nervous system. In mouse hairy skin, hair follicle-associated longitudinal lanceolate complexes, which are end organs comprising LTMR axonal endings that intimately associate with terminal Schwann cell (TSC) processes, mediate LTMR responses to hair deflection and skin indentation. Here, we characterized developmental steps leading to the formation of Aß rapidly adapting (RA)-LTMR and Aδ-LTMR lanceolate complexes. During early postnatal development, Aß RA-LTMRs and Aδ-LTMRs extend and prune cutaneous axonal branches in close association with nascent TSC processes. Netrin-G1 is expressed in these developing Aß RA-LTMR and Aδ-LTMR lanceolate endings, and Ntng1 ablation experiments indicate that Netrin-G1 functions in sensory neurons to promote lanceolate ending elaboration around hair follicles. The Netrin-G ligand (NGL-1), encoded by Lrrc4c, is expressed in TSCs, and ablation of Lrrc4c partially phenocopied the lanceolate complex deficits observed in Ntng1 mutants. Moreover, NGL-1-Netrin-G1 signaling is a general mediator of LTMR end organ formation across diverse tissue types demonstrated by the fact that Aß RA-LTMR endings associated with Meissner corpuscles and Pacinian corpuscles are also compromised in the Ntng1 and Lrrc4c mutant mice. Thus, axon-glia interactions, mediated in part by NGL-1-Netrin-G1 signaling, promote LTMR end organ formation.

Precise Control of Metal Active Sites of Metal-Organic Framework Nanozymes for Achieving Excellent Enzyme-Like Activity and Efficient Pancreatitis Therapy.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease that can lead to the development of systemic inflammatory response syndrome and its progression to severe acute pancreatitis. Hence, there is an urgent need for the rational design of highly efficient antioxidants to treat AP. Herein, an optimized Cu-based metal-organic framework (MOF) nanozyme with exceptional antioxidant activity is introduced, designed to effectively alleviate AP, by engineering the metal coordination centers in MN2Cl2 (M = Co, Ni, Cu). Specifically, the Cu MOF, which benefits from a Cu active center similar to that of natural superoxide dismutase (SOD), exhibited at least four times higher SOD-like activity than the Ni/Co MOF. Theoretical analyses further demonstrate that the CuN2Cl2 site not only has a moderate adsorption effect on the substrate molecule •OOH but also reduces the dissociation energy of the product H2 O2 . Additionally, the Cu MOF nanozyme possesses the excellent catalase-like activity and •OH removal ability. Consequently, the Cu MOF with broad-spectrum antioxidant activity can efficiently scavenge reactive oxygen species to alleviate arginine-induced AP. More importantly, it can also mitigate apoptosis and necrosis of acinar cells by activating the PINK1/PARK2-mediated mitophagy pathway. This study highlights the distinctive functions of tunable MOF nanozymes and their potential bio-applications.

ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway.

The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REGγ has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REGγ expression and activated the REGγ-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REGγ promoter region histone H3K27ac, and subsequently induced REGγ expression. Lastly, enhanced acetylation of the REGγ promoter region histone H3K27ac resulted in upregulated REGγ expression, activation of the REGγ-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REGγ knockdown reversed these effects. ACLY and REGγ may serve as potential biomarkers and clinical therapeutic targets for HCC.

Effects of diets with different amino acid release characteristics on the gut microbiota and barrier function of weaned pigs.

BACKGROUND: The absorption and utilization of proteins by animals is affected by the amino acid (AA) release characteristics of their diets. In the present study, we aimed to determine the effects of diets with various amino acid release characteristics on the intestinal barrier function and diversity of gut microbiota of weaned pigs. RESULTS: Forty-eight pigs (7.45 ± 0.58 kg) were fed with diets having different amino acid release characteristics during a period of 28 days. We used a 2 × 3 full-factor (two protein levels and three protein sources with differing amino acid release characteristics) experimental design, with normal (standard terminal ileal digestibility of 17.5%) or low (standard terminal ileal digestibility of 14.9%) protein levels as the first factor. Casein (CAS), corn gluten meal (CGM) and a MIX diet were used as protein sources. Due to the more balanced release of amino acids, the diamine oxidase (DAO) concentrations in the CAS and MIX groups were significantly lower than those in the CGM group (P < 0.05); Reducing the dietary protein content from 17.5% to 14.9% had no significant effects on the levels of serum DAO or D-lactic acid. By contrast, it increased the microbial diversity (chao1 and ACE values) and the number of Lactobacillus in the jejunum (P < 0.05). The CAS-containing diet and the MIX diet resulted in significantly higher microbial diversity (Simpson and Shannon) than the CGM-containing diet in the jejunum. CONCLUSION: The balanced release of amino acids in CAS and MIX diets maintained intestinal barrier function and increased gut microbiota diversity. These findings could potentially provide a scientific reference for the rational preparation of piglet feed.

Interaction of total dissolved gas supersaturation and suspended sediment on swimming performance of bighead carp (Hypopthalmichthys nobilis).

When dams discharge floodwaters, the river downstream often becomes supersaturated in total dissolved gases (TDG) and contains high volumes of suspended sediments (SS). Supersaturated TDG and high SS concentrations in water may affect fish physiologically in ways that manifest in swimming performance. Despite increasing awareness of the separate effects of TDG supersaturation and SS, knowledge about their synergistic effects remains unknown. To explore the interactive effects of TDG and SS on the swimming performance of bighead carp, the juveniles were exposed to 100, 110, 115, 120, 125, 130, 135, and 140% of TDG-supersaturated water with SS concentrations of 0, 50, 100, and 150 mg/L, respectively, and the critical swimming ability speed (Ucrit ) and burst swimming ability speed (Uburst ) were measured. The results indicated that the swimming ability (Ucrit and Uburst ) decreased when TDG levels and SS concentrations increased. TDG and SS did not interact significantly to decrease both Ucrit and Uburst . In contrast, exposure to TDG alone significantly decreased both Ucrit and Uburst , whereas exposure to SS alone decreased only Uburst . In addition, our results suggested that there was a negative linear relationship between TDG and fatigue time. Swimming ability can decline significantly due to high TDG levels (>130%). Therefore, high TDG levels (>130%) should be restricted during reservoir operation to prevent the stress caused by TDG.

CDK14/ß-catenin/TCF4/miR-26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo.

INTRODUCTION: Chemotherapy and radiotherapy have been reported to be basically ineffective for pancreatic ductal adenocarcinoma patients; thus, gene therapy might provide a novel approach. CDK14, a new oncogenic member of the CDK family involved in the pancreatic cancer cell response to gemcitabine treatment, has been reported to be regulated by microRNAs. In the present study, we aimed to investigate whether miR-26b regulated CDK14 expression to affect the phenotype of pancreatic cancer cells. METHODS: Overexpression or knockdown of CDK14 or miR-26b was generated in pancreatic cancer cell lines and the function of CDK14 and miR-26b on cell phenotype and the Wnt signaling pathway was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and transwell assays, as well as a xenograft model and western blotting. The predicted binding site between the 3'-untranslated region of CDK14 and miR-26b, miR-26b promoter and TCF4 was verified by luciferase or chromatin immunoprecipitation assays. RESULTS: CDK14 overexpression inhibited p-GSK3ß, whereas it promoted p-LRP6, the nuclear translocation of ß-catenin and the transactivation of TCF4 transcription factor, thus promoting pancreatic cancer cell aggressiveness. miR-26b directly targeted CDK14 and inhibited CDK14 expression. In vitro and in vivo, miR-26b overexpression inhibited, and CDK14 overexpression promoted, cancer cell aggressiveness; CDK14 overexpression partially attenuated the miR-26b overexpression effects on cancer cells. The effects of miR-26b overexpression on tumor growth and the Wnt/ß-catenin/TCF4 signaling were partially reversed by CDK14 overexpression. TCF4 inhibited the expression of miR-26b by targeting its promoter region. CONCLUSIONS: CDK14, ß-catenin, TCF4 and miR-26b form a positive feedback regulation for modulating pancreatic cancer cell phenotypes in vitro and tumor growth in vivo.

Synthetic oleanane triterpenoid derivative CDDO-Me disrupts cellular bioenergetics to suppress pancreatic ductal adenocarcinoma via targeting SLC1A5.

To investigate the potential antitumor activity of synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) in pancreatic ductal adenocarcinoma (PDAC), MTT cytotoxicity assay, and xenograft nude mice assay were performed to evaluate tumor growth in vitro and in vivo. Seahorse XFe96 bioenergetics analyzer was applied to determine aerobic glycolysis and mitochondrial respiration. Western blot and quantitative reverse transcription-polymerase chain reactions are used to detect protein and messenger RNA transcripts of SLC1A5 and metabolic enzymes. We confirmed the strong antitumor activity of CDDO-Me in suppressing PDAC growth. Mechanistically, we demonstrated CDDO-Me induced mitochondrial respiration and aerobic glycolysis dysfunction. We also verified CDDO-Me downregulated glutamine transporter SLC1A5, resulting in excessive reactive oxygen species (ROS) levels that suppressed tumor growth. Moreover, we confirmed that SLC1A5 depletion reduced the ratio of glutathione/oxidized glutathione. We also found CDDO-Me could inhibit N-linked glycosylation of SLC1A5, which promotes protease-mediated degradation. Finally, we confirmed SLC1A5 was significantly overexpressed in PDAC and closely correlated with the poor prognosis of PDAC patients. Our work uncovers CDDO-Me is effective at suppressing PDAC cell growth in vitro and in vivo and illuminates CDDO-Me caused excessive ROS and cellular bioenergetics disruption which contributed to CDDO-Me inhibited PDAC growth. Our data highlights CDDO-Me could be considered a potential compound for PDAC therapy, and SLC1A5 could be a novel biomarker for PDAC patients.

Using recycled coffee grounds for the synthesis of ZIF-8@BC to remove Congo red in water.

Around 6.6 million tons of spent coffee is produced per year, resulting in resources loss and potential environmental risks. Hence, a green technique is required to reuse the spent coffee grains. In this study, coffee grounds were burnt at 900 °C to generate the biochar (BC) for the synthesis of the porous adsorbent (ZIF-8 @BC) by growing ZIF-8 on the surface of BC. We applied the well-prepared ZIF-8 @BC to remove Congo red (CR) in water. The maximum adsorption capacity of ZIF-8 @BC on Congo red in water was up to 1080.4 mg/g, which was significantly higher than that of many different types of BCs reported in previous studies. The reasons for its highly efficient adsorption of CR probably was attributed to metal ions and coordinatively unsaturated sites in the material. Also, BC enabled the less aggregation of ZIF-8 to provide sufficient specific surface area for CR adsorption. From the analysis of the pseudo-second-order kinetic model and Langmuir model, the adsorption of ZIF-8 @BC on CR was a homogeneously chemical adsorption process regulated by electrostatic interaction, π-π stacking and metal coordination.

LincRNA-EPS alleviates severe acute pancreatitis by suppressing HMGB1-triggered inflammation in pancreatic macrophages.

Acute pancreatitis (AP), an inflammatory disorder of the pancreas with a high hospitalization rate, frequently leads to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). However, therapeutic targets for effective treatment and early intervention of AP are still urgently required to be identified. Here, we have observed that the expression of pancreatic lincRNA-EPS, a long intergenic non-coding RNA, is dynamically changed during both caerulein-induced AP (Cer-AP) and sodium taurocholate-induced severe AP (NaTc-SAP). The expression pattern of lincRNA-EPS is negatively correlated with the typical inflammatory genes such as IL-6, IL-1ß, CXCL1, and CXCL2. Further studies indicate that knockout of lincRNA-EPS aggravates the pathological symptoms of AP including more induction of serum amylase and lipase, severe edema, inflammatory cells infiltration and acinar necrosis in both experimental AP mouse models. Besides these intrapancreatic effects, lincRNA-EPS also protects against tissue damages in the extra-pancreatic organs such as lung, liver, and gut in the NaTc-SAP mouse model. In addition, we have observed more serum pro-inflammatory cytokines TNF-α and IL-6 in the lincRNA-EPS-/- NaTc-SAP mice and more extracellular HMGB1 around injured acinar cells in the pancreas from lincRNA-EPS-/- NaTc-SAP mice, compared with their respective controls. Pharmacological inhibition of NF- κ B activity by BAY11-7082 significantly abolishes the suppressive effect of lincRNA-EPS on TLR4 ligand-induced inflammatory genes in macrophages. Our study has described a protective role of lincRNA-EPS in alleviating AP and SAP, outlined a novel pathway that lincRNA-EPS suppresses HMGB1-NF- κ B-dependent inflammatory response in pancreatic macrophages and provided a potential therapeutic target for SAP.

Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2.

BACKGROUND: Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown. METHODS: The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions. RESULTS: Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3' UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT. CONCLUSIONS: Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC.

Chlorogenic acid depresses cellular bioenergetics to suppress pancreatic carcinoma through modulating c-Myc-TFR1 axis.

Pancreatic ductal adenocarcinoma (PDAC) is severe malignant tumor in human, the outcomes of PDAC is extremely poor. Here, we evaluated the potential anti-tumor activity of chlorogenic Acid (CA) in PDAC. Here, we found CA was effective to suppress PDAC cell growth in vitro and in vivo. Importantly, we found overall oxygen consumption rate was significantly decreased in CA dose-dependent manner. We also found glycolysis reverse was decreased in CA-treated cells, while basal glycolysis and glycolytic capacity were not significantly changed. Mechanistically, we demonstrated TFR1 could be a novel downstream target of CA, which is essential for PDAC cell growth and cellular bioenergetics maintenance. Furthermore, we validated that CA-reduced c-Myc resulted to down-regulation of TFR1, which contributes to mitochondrial respiration dysfunction and cell growth delay. Together, this study indicates that CA suppresses PDAC cell growth through targeting c-Myc-TFR1 axis and suggests CA could be considered as a promising compound for PDAC treatment.

The Mechanism of miR-222 Targets Matrix Metalloproteinase 1 in Regulating Fibroblast Proliferation in Hypertrophic Scars.

This study aimed to investigate the value of miR-222 in hypertrophic scars (HS). Specific mechanisms were used to measure the level of miR-222, while MTT assay, flow cytometry, western blot and qRT-PCR were employed to detect the relative proteins after fibroblasts were transfected with the miR-222 mimic/inhibitor. The direct target of miR-222 was determined by Dual-Luciferase Reporter assay. Furthermore, qRT-PCR and western blot were employed to detect the matrix metalloproteinase 1 (MMP1) RNA/protein after fibroblasts were transfected with the miR-222 mimic/inhibitor. These results revealed that miR-222 was significantly upregulated in HS fibroblasts. The overexpression of miR-222 enhanced the HS fibroblast proliferation, increased the cell population in the S phase, inhibited the cell apoptosis, enhanced the expression levels of Col1A1, Col3A1 mRNA/protein, proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E1 and CDK1 and reduced the expression levels of cleaved caspase-3/9. However, the miR-222 suppression triggered opposite effects. Furthermore, miR-222 played a regulatory role in HS by negatively regulating its target gene MMP1 by binding with its 3'-untranslated region. The overexpression of MMP1 reduced the expression levels of PCNA and cyclin D1, but enhanced the expression levels of cleaved caspase-3. Therefore, MiR-222 and MMP1 have potential value for HS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Antitumor activity and combined inhibitory effect of ceritinib with gemcitabine in pancreatic cancer.

Pancreatic cancer (PC) is predominantly incurable and is primarily treated with gemcitabine, but drug resistance commonly develops. Thus, new medicines are needed. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) with antitumor activity in various cancers. However, studies involving ceritinib for the treatment of PC are inadequate. We analyzed the combined effects of ceritinib and gemcitabine on PC and their mechanism of action. Three PC cell lines were used to evaluate the antitumor effects of ceritinib combined with gemcitabine. We analyzed cell viability using CCK-8 assays, determined apoptosis levels through flow cytometry, and analyzed autophagy and cell signaling pathways by Western blotting and tissue array analysis with samples from xenograft models. Ceritinib strongly inhibited the proliferation of PC cells in a dose-dependent manner, induced apoptosis, and inhibited autophagy and cell migration by regulating relevant factors. Ceritinib in combination with gemcitabine exhibited significant growth inhibition and additive antitumor effects in vitro. In vivo, gemcitabine and ceritinib reduced tumor size by up to 30%. In our study, ALK was shown to be highly expressed in various PC cells and tissues. Ceritinib strongly inhibited the levels of activated ALK in PC cells with subsequent effects on the downstream mediators STAT3, AKT, and ERK. In addition, ceritinib inhibited tumor progression in xenograft models. Overall, our research shows that ceritinib inhibits the ALK signaling pathway, leading to cell growth/angiogenesis inhibition in PC and the induction of apoptosis. We recommend using ceritinib as a new treatment for PC.NEW & NOTEWORTHY These data proved that ceritinib inhibits the anaplastic lymphoma kinase signaling pathway, leading to cell growth/angiogenesis inhibition and the induction of apoptosis by inhibiting STAT3, AKT, and ERK pathway in pancreatic cancer (PC). We recommend using ceritinib as a new treatment for PC.

Experimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approach.

Liver cancer is a worldwide disease, and, currently, due to the poor prognostic and therapeutic options of liver cancer, we investigated the T cell epitopes as potential therapeutic vaccine candidates to get the benefit of experimental processes and utilize the complete ability of the immune system compared with other artificial ex vivo proliferation of T cells. Activation of T cells targets and kills several tumors, developing a strong rationale for the improvement of immunotherapeutic strategies to cancer therapy. To predict T cell epitopes for liver cancer, we designed a comprehensive immunoinformatics framework involving data mining, immunogenicity prediction, functional proteomic analysis, conservation studies, molecular modeling, and in vivo validation analysis. We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) I molecules to control the cancerous activity. Five extracellular antigenic proteins, including complement protein (C6), serotransferrin, coagulation factor XIII B, serum albumin (ALB), and prothrombin, were identified. We predicted and synthesized T cell epitopes to human leukocytes antigen-A*01:01 allele of MHC class I molecule. The hematological assay and IgG ELISA showed that C6 and ALB epitopes induced the production of lymphocytes, granulocytes, and peptide-specific IgG in immunized rats. We observed substantial high levels of granzymes B in serum samples of C6 and ALB compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer.NEW & NOTEWORTHY We observed substantial high levels of granzymes B in serum samples of component C6 (C6) and albumin (ALB) compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer.

Pd(II)-Catalyzed Direct γ-C(sp3)-H Arylation between Free ß2-Amino Esters and ß3-Amino Esters and Aryl Iodides Using a Catalytic Transient Directing Group.

Pd(II)-catalyzed direct γ-C(sp3)-H arylation coupling with free ß2-amino esters and ß3-amino esters using a commercially available catalytic transient directing group has been developed. This approach features high efficiency, broad substrate tolerance, easily accessible starting materials, and mild reaction conditions.

Ultrasound Backscatter Envelope Statistics Parametric Imaging for Liver Fibrosis Characterization: A Review.

Early detection and diagnosis of liver fibrosis is of critical importance. Currently the gold standard for diagnosing liver fibrosis is biopsy. However, liver biopsy is invasive and associated with sampling errors and can lead to complications such as bleeding. Therefore, developing noninvasive imaging techniques for assessing liver fibrosis is of clinical value. Ultrasound has become the first-line tool for the management of chronic liver diseases. However, the commonly used B-mode ultrasound is qualitative and can cause interobserver or intraobserver difference. Ultrasound backscatter envelope statistics parametric imaging is an important group of quantitative ultrasound techniques that have been applied to characterizing different kinds of tissue. However, a state-of-the-art review of ultrasound backscatter envelope statistics parametric imaging for liver fibrosis characterization has not been conducted. In this paper, we focused on the development of ultrasound backscatter envelope statistics parametric imaging techniques for assessing liver fibrosis from 1998 to September 2019. We classified these techniques into six categories: constant false alarm rate, fiber structure extraction technique, acoustic structure quantification, quantile-quantile probability plot, the multi-Rayleigh model, and the Nakagami model. We presented the theoretical background and algorithms for liver fibrosis assessment by ultrasound backscatter envelope statistics parametric imaging. Then, the specific applications of ultrasound backscatter envelope statistics parametric imaging techniques to liver fibrosis evaluation were reviewed and analyzed. Finally, the pros and cons of each technique were discussed, and the future development was suggested.

A Novel Silicone Fixation Dressing: A Possibly Ideal Method for Drainage Tube Fixation.

Introduction. Some issues of drainage tube after surgery, such as unplanned extubation and local pain, have been puzzling surgeons. Methods. We designed a product that uses a two-way wrap technique to fix the tube in place, absorption pad to absorb excess fluid spill around the tube and a restickable silicone adhersive property which maintains the adhersive strength of the fixation for at least 10 days. Result. The preliminary clinical studies results showed a possibly better fixation property by giving the drainage tube a firmer hold, easy to use device and a relatively painless noninvasive procedure method as compared to the traditional drainage fixation. Conclusion. The novel silicone fixation dressing has graced surgery with innovation by improving on the flaws associated with the traditional drain fixation. Making it a possibly ideal method for drainage tube fixation and highly recommended for clinical use.

LncRNA H19/miR-194/PFTK1 axis modulates the cell proliferation and migration of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge due to its high mortality and morbidity; gene therapy might be a promising treatment for PDAC. The critical role of Wnt-signaling pathway in cancer pathogenesis has been widely recognized; cyclin-dependent kinase 14 (CDK14, PFTK1)-induced low-density lipoprotein receptor-related proteins 5/6 (LRP5/6) phosphorylation is an important issue in Wnt-signaling activation. Long noncoding RNA (LncRNA)-microRNA (miRNA)-messenger RNA (mRNA) modulating the pathogenesis of cancers has been regarded as a major mechanism. In the current study, upregulated lncRNAs positively correlated with PFTK1 were analyzed and selected using The Cancer Genome Atlas (TCGA) database. Of them, lncRNA H19 can activate Wnt signaling in cancers. In PDAC tissues, the expression of H19 and PFTK1 were upregulated; H19 knockdown suppressed the cell proliferation and migration of PDAC, while PFTK1 overexpression partially attenuated the suppressive effect of H19 knockdown. As analyzed by TCGA and predicted by online tools, miR-194 was negatively correlated with PFTK1 and might bind to both H19 and PFTK1, which was further confirmed by luciferase reporter and RNA immunoprecipitation assays. Moreover, the effect of H19 knockdown on PFTK1 protein and the cell proliferation and migration could be partially reversed by miR-194 inhibition; H19/miR-194 axis modulated PDAC cell proliferation and migration through PFTK1 downstream Wnt signaling. Results suggested that rescuing miR-194 expression in PDAC can inhibit lncRNA H19 and PFTK1 expression, subsequently suppressing PDAC cell proliferation and migration. Due to the complexity of the lncRNA-miRNA-mRNA network, further in vivo experiments examining potential side effects are needed in future study to explore the clinical application of these findings.

Protective effects of maresin 1 against inflammation in experimentally induced acute pancreatitis and related lung injury.

Severe acute pancreatitis (SAP) is an inflammatory disorder that progresses with local and systemic difficulties accompanied by a relatively high mortality rate. In recent years, maresin 1 (MaR1) has been shown to be a macrophage mediator with effective proresolving and anti-inflammatory properties that prevents the occurrence of various inflammatory conditions. The purpose of this study was to investigate the role of MaR1 in SAP and related lung injury. Experimental SAP was induced in mice with a combination of cerulean and lipopolysaccharide. MaR1 was administered 30 min before the primary injection of cerulean. Biochemical markers and histological injury scores were used to evaluate the severity of acute pancreatitis. To determine the degree of inflammation, serum cytokines and myeloperoxidase activity in pancreas and lung tissues were measured. Western blot analysis detected the activation of NF-κB. After MaR1 pretreatment, the activities of amylase, lipase, TNF-α, IL-1ß, and IL-6 were decreased in serum, and the myeloperoxidase activity both in pancreas and in lung tissues significantly decreased, whereas the activity of anti-inflammatory cytokine IL-10 in serum was increased. MaR1-pretreated mice reduced the activation of pancreatic NF-κB and decreased the severity of pancreatic and lung-related injuries. These results confirm that MaR1 alleviated inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimentally induced acute pancreatitis and exerted anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of SAP.NEW & NOTEWORTHY These results provided us evidence to confirm that maresin 1 (MaR1) can alleviate inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimental induced acute pancreatitis and exerts certain anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of severe acute pancreatitis.