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Nanotechnology is associated with the development of particles in the nano-size range that can be used in a wide range of applications in the medical field. It has gained more importance in the pharmaceutical research field particularly in drug delivery, as it results in enhanced therapeutic drug performance, improved drug solubility, targeted drug delivery to the specific sites, minimized side effects, and prolonged drug retention time in the targeted site. To date, the application of nanotechnology continues to offer several benefits in the treatment of various chronic diseases and results in remarkable improvements in treatment outcomes. The use of nano-based delivery systems such as liposomes, micelles, and nanoparticles in pulmonary drug delivery have shown to be a promising strategy in achieving drug deposition and maintained controlled drug release in the lungs. They have been widely used to minimize the risks of drug toxicity in vivo. In this review, recent advances in the application of nano- and micro-based delivery systems in pulmonary drug delivery for the treatment of various pulmonary diseases, such as lung cancer, asthma, and chronic obstructive pulmonary disease, are highlighted. Limitations in the application of these drug delivery systems and some key strategies in improving their formulation properties to overcome challenges encountered in drug delivery are also discussed.

We extracted, purified, and characterized three neutral and three acidic polysaccharides from the roots, stems, and leaves of

Purpose: To investigate whether hydrogen-oxygen (67%–33%) therapy could improve the postoperative pulmonary function, recovery, complications, inflammatory reactions, and oxidative stress in patients undergoing lung surgery.Methods: We performed a prospective, randomized, single-blind, controlled clinical trial between December 2020 and December 2021. Eligible patients received either a lobectomy or sublobar resection. Postoperatively, they had 2-hour hydrogen-oxygen therapy (group H) or oxygen therapy (group C) daily, for three consecutive days. The pulmonary functions, recovery, pain intensity, oxygen saturation, inflammatory cytokines, and anti-oxidative markers were documented.Results: A total of 66 patients were analyzed, with 33 patients in each group. Both groups had decreased postoperative pulmonary functions, but group H had significantly better postoperative pulmonary functions than group C (forced vital capacities were 1.4±0.5 and 1.0±0.4 L and forced expiratory volumes in the first second were 1.1±0.3 and 0.9±0.3 L in group H and C, respectively (both PConclusion: Hydrogen-oxygen therapy could improve postoperative pulmonary functions, decrease pain intensity, accelerate recovery, and shorten the length of the hospital stay in patients who have undergone lung resection, which may be related to its anti-inflammatory and anti-oxidative effects. Trial registration: The Chinese Clinical Trial Registry (registration number ChiCTR2100042101)，the date of registration was January,13,2021.

Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific antigen (PSA) test for PCa remains controversial. Therefore, the development of more effective non-invasive biomarkers for PCa is necessary. The present study evaluated the diagnostic value of microRNA (miR)-20b-5p in PCa. Tissue miR-20b-5p expression levels and their correlation with clinical parameters were assessed using The Cancer Genome Atlas (TCGA) datasets, and the diagnostic value of the miR-20b-5p expression levels in PCa tissues was assessed using receiver operating characteristic curve analysis. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the relative expression levels of miR-20b-5p in PCa tissues compared with benign prostate hyperplasia (BPH) tissues. In addition, miR-20b-5p expression levels in PCa cell lines and non-tumorigenic prostate epithelial cells were compared. In this study, exosomes were extracted from the prostatic fluid as a source of liquid biopsy for the detection of PCa. The prostatic fluid exosomal miR-20b-5p expression levels between patients with PCa and the biopsy-negative patients were compared, and the diagnostic efficiency of prostatic fluid exosomal miR-20b-5p expression levels in PCa was compared with PSA and with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator. The mechanism by which miR-20b-5p may function in PCa was assessed using bioinformatic analysis and validation experiments. miR-20b-5p was expressed at a markedly higher level in PCa tissues compared with normal prostate tissues with high diagnostic efficiency (area under the curve: 0.826). The expression levels of miR-20b-5p were also significantly higher in PCa tissues compared with BPH tissues; similarly, miR-20b-5p was more highly expressed in PCa cells compared with non-tumorigenic prostate epithelial cells. Prostatic fluid exosomal miR-20b-5p expression levels in patients with PCa were significantly higher compared with confirmed to be biopsy-negative, and the diagnostic performance of miR-20b-5p was superior to PSA and ERSPC risk calculator. The results of RT-qPCR and western blotting following transfection of DU145 cells with miR-20b-5p mimics and inhibitor showed that miR-20b-5p reduced the expression of retinoblastoma-associated protein 1 (RB1). Therefore, RB1 may be a significant target gene for miR-20b-5p. In conclusion, the present study demonstrated that miR-20b-5p was upregulated in PCa at the tissue and cellular levels, as well as in prostatic fluid exosomes. Therefore, miR-20b-5p may be a promising early diagnostic biomarker for PCa and an important tool to guide the decision-making of prostate biopsy.

Glycogen synthase kinase 3 (Gsk3) α and β are both constitutively active and inhibited upon stimulation by N-terminal serine phosphorylation. Although roles of active Gsk3 in liver ischemia reperfusion injury (IRI) have been well appreciated, whether Gsk3 N-terminal serine phosphorylation has any functional significance in the disease process remains unclear. In a murine liver partial warm ischemia model, we studied Gsk3 N-terminal serine mutant knock-in (KI) mice and showed that liver IRI was decreased in Gsk3αS21A but increased in Gsk3βS9A mutant KI mice. Bone marrow chimeric experiments revealed that the Gsk3α, but not β, mutation in liver parenchyma protected from IRI, and both mutations in bone marrow–derived cells exacerbated liver injuries. Mechanistically, mutant Gsk3α protected hepatocytes from inflammatory (TNF-α) cell death by the activation of HIV-1 TAT-interactive protein 60 (TIP60)–mediated autophagy pathway. The pharmacological inhibition of TIP60 or autophagy diminished the protection of the Gsk3α mutant hepatocytes from inflammatory cell death in vitro and the Gsk3α mutant KI mice from liver IRI in vivo. Thus, Gsk3 N-terminal serine phosphorylation inhibits liver innate immune activation but suppresses hepatocyte autophagy in response to inflammation. Gsk3 αS21, but not βS9, mutation is sufficient to sustain Gsk4 activities in hepatocytes and protect livers from IRI via TIP60 activation.

Farnesoid X receptor (FXR) is the nuclear receptor of bile acids and is involved in innate immune regulation. FXR agonists have been shown to protect multiple organs from inflammatory tissue injuries. Because liver expresses high levels of FXR, we explored the potential therapeutic benefits and underlying mechanisms of pharmacologic FXR activation in a murine model of partial liver warm ischemia. Pretreatment of mice with FXR agonist 3-(2,6-dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole (GW4064) attenuated liver ischemia/reperfusion injuries (IRIs) in wild-type but not FXR knockout mice. Posttreatment with GW4064 facilitated liver recovery from IRI. Mechanistically, Kupffer cells (KCs) expressed much higher levels of FXR than bone marrow-derived macrophages (BMMs). Pretreatment of KCs but not BMMs with GW4064 resulted in lower tumor necrosis factor α but higher interleukin-10 expressions following toll-like receptor stimulation. FXR-targeted gene small heterodimer partner (SHP) was critical for the regulation of KC response by GW4064. In vivo, the depletion of KCs but not cluster of differentiation (CD) 11b+ cells or knockdown of SHP diminished the immune regulatory effect of GW4064 in liver IRI. Thus, FXR activation protects liver from IRI by up-regulating SHP in KCs to inhibit the liver proinflammatory response.

Traditional bioelectrochemical systems (BESs) coupled with stripping units for ammonia recovery suffer from an insufficient supply of electron acceptors due to the low solubility of oxygen. In this study, we proposed a novel strategy to efficiently transport the oxidizing equivalent provided at the stripping unit to the cathode by introducing a highly soluble electron mediator (EM) into the catholyte. To validate this strategy, we developed a new kind of iron complex system (tartrate-EDTA-Fe) as the EM. EDTA-Fe contributed to the redox property with a midpoint potential of -0.075 V (vs. standard hydrogen electrode, SHE) at pH 10, whereas tartrate acted as a stabilizer to avoid iron precipitation under alkaline conditions. At a ratio of the catholyte recirculation rate to the anolyte flow rate (R

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells. Recent studies showed that Signal Transducer and Activator of Transcription 3 (STAT3), which plays an important role in cell survival, proliferation, differentiation, angiogenesis, and immune responses, is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions. In addition, STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production, thereby exacerbating the condition of psoriasis. Alantolactone (ALT) is a sesquiterpene lactone compound that could selectively suppress STAT3 activation, but its effectiveness and application in psoriasis treatment have not been determined. In this study, we developed ALT loaded chitosan/hyaluronic acid nanoparticles (CHALT), and investigated its therapeutic potential for psoriasis therapy. CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrial membrane potential, and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line. In an Imiquimod (IMQ)-induced psoriasis model, the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis. In addition, it was found that CHALT restricted the recruitment of immune cells. These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

Background A major discrepancy between clinical and most experimental settings of liver ischemia-reperfusion injury (IRI) is the allogenicity. Methods In the current study, we first established a murine model of allogeneic orthotopic liver transplantation with extended cold ischemia time (18 h). Roles of CD4 T cells in the pathogenesis of IRI in liver allografts were determined using a depleting anti-CD4 antibody. The clinical relevance of CD4 as a marker of liver IRI was analyzed retrospectively in 55 liver transplant patients. Results CD4 depletion in both donors and recipients resulted in the most effective protection of liver allografts from IRI, as measured by serum transaminase levels and liver histology. CD4 depletion inhibited IR-induced intragraft neutrophil/macrophage infiltration and proinflammatory gene expressions. Quantitative reverse-transcriptase polymerase chain reaction analysis of human liver biopsies (2 h postreperfusion) revealed that posttransplant, rather than pretransplant, CD4 transcript levels correlated positively with proinflammatory gene expression profile. When we divided patients into subgroups according to intragraft CD4 levels, the high CD4 cohort developed a more severe hepatocellular damage than that with low CD4 levels. Conclusions CD4 T cells play a key pathogenic role in IRI of allogeneic liver transplants, and intragraft CD4 levels in the early postreperfusion phase may serve as a potential biomarker and therapeutic target to ameliorate liver IRI and improve orthotopic liver transplantation outcomes.

Hu JC, Wang Q, Jiang LX, et al. Onco Targets Ther. 2018;11:6259–6269. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figure 3 and Figure 5. The authors responded to our queries but were unable to provide an explanation for the alleged image duplication and were unable to verify their original data and have therefore agreed to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

BACKGROUND Organ-associated pseudosarcomatous myofibroblastic proliferation (PMP) is a very rare disorder. In the urogenital tract, PMP preferentially involves the urinary bladder; kidney involvement is rare. Here, we report a rare case of PMP with ossification in the lower pole of the kidney, which mimics urothelial carcinoma or an osteogenic tumor. CASE SUMMARY A Chinese man was admitted to our hospital due to intermittent hematuria for more than 1 mo. Enhanced renal computed tomography revealed a mass in the left renal pelvis and upper ureter. The preoperative clinical diagnosis was renal pelvic carcinoma, determined by imaging examination and biopsy. After a standard preparation for surgery, the patient underwent retroperitoneoscopic radical nephroureterectomy. The operative findings were an extensive renal tumor (6 cm × 4.5 cm × 4.5 cm) invading the lower pole of the kidney and upper ureter. The final pathological diagnosis was organ-associated PMP with ossification. After 6-mo follow-up, no recurrence or metastasis was found. CONCLUSION This case of PMP was unusual for its mimicking renal pelvic carcinoma in imaging examinations, making biopsy necessary.

Macrophage polarization is one of the main factors contributing to the proinflammatory milieu of transplanted islets. It causes significant islet loss. Bilirubin exhibits protective effects during the islet transplantation process, but the mode of delivering drugs along with the islet graft has not yet been developed. In addition, it remains unclear whether bilirubin or its derivatives can modulate macrophage polarization during islet transplantation. Therefore, this study aimed to develop an e-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets for protection and to explore its macrophage modulation activities. In in vitro studies, the PLL-BR was shown to tightly adhere to the islet surface. It also exhibited enhanced cytoprotective effects against oxidative and inflammatory conditions by promoting M2-type macrophage polarization. In in vivo studies, the PLL-BR-protected islets successfully prolonged the euglycemia period in diabetic mice and accelerated the blood glucose clearance rate by maintaining the insulin secretion function. Compared to the untreated islets, the PLL-BR-encapsulated islets induced anti-inflammatory responses that were characterized by elevated levels of M2 macrophage markers and local vascularization. In conclusion, PLL-BR can be used as a tool for reprograming macrophage polarization while providing a more efficient immune protection for transplanted islets. Statement of significance Macrophage polarization is one main factor that caused significant loss of transplanted islets. Bilirubin possesses protective effects toward pancreatic islet, but how to deliver the drug along with the islet graft has not yet been harnessed. More importantly, whether bilirubin or its derivatives could modulate macrophage polarization during the host rejections has also not been answered. In this study, we developed an e-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets and explore its role in macrophage modulation activities. PLL-BR could attach to the surface of islets and exerted high oxidation resistance and anti-inflammatory effect. For the first time, we demonstrate that bilirubin and its derivatives effectively promoted the M2-type macrophage polarization, and optimize the immune microenvironment for islets survival and function.

Rationale: Photothermal therapy employs the photoabsorbers to generate heat under the near-infrared (NIR) irradiation for thermal tumor ablation. However, NIR irradiation might damage the adjacent tissue due to the leakage of the photoabsorbers and the residual materials after treatment might hinder the local healing process. A bifunctional hydrogel that holds both photothermal property and potent pro-healing ability provides a viable option to resolve this issue. Methods: In this study, we developed a bioinspired green hydrogel (BVSF) with the integration of bioproduct biliverdin into natural derived silk fibroin matrix for antiglioma photothermal therapy and wound healing. Results: The BVSF hydrogel possessed excellent and controllable photothermal activity under NIR irradiation and resulted in effective tumor ablation both in vitro and in vivo. Additionally, the BVSF hydrogel exerted anti-inflammatory effects both in vitro and in vivo, and stimulated angiogenesis and wound healing in a full-thickness defect rat model. Conclusion: Overall, this proof-of-concept study was aimed to determine the feasibility and reliability of using an all-natural green formulation for photothermal therapy and post-treatment care.

The weakly bound nucleus 29F locates near the neutron drip line. Experiments have confirmed that it is the heaviest two-neutron halo nucleus discovered up to now. To understand the halo structure in 29F, we explore the weakly bound and resonant levels close to the Fermi surface with the complex momentum representation method. Not only the narrow resonances and the broad resonances. Since the broad resonance 2p 3/2 is disclosed, the p − f inversion and N = 20 shell gap quenching are found. The last valence neutron can occupy the weakly bound level 1/2[310], composed mainly of p 3/2–component, or the 1/2[211], composed mainly of s 1/2–component. Since the wavefunctions of p and s–components extend to a large range in the coordinate space, which results in the density distributions of the levels 1/2[310] and 1/2[211] being considerably diffuse. This is the most likely cause of halo formation in 29F and the halo may be formed by the p–component, s–component, or their mixtures by pairing correlations.

The fast and reliable connection between modules plays an essential role in modular steel buildings to ensure the structure's integrity. Using complete bolt assembly can better improve the efficiency of on-site construction. To study the seismic ductility reduction of connections and obtain the measures suitable for protecting the beam-column weld in connections, full-scale experiments on the connections were carried out under monotonic and cyclic loading. The failure modes, the static and hysteretic performance of the connections were manifested. The experimental results indicated the satisfactory flexural performance and the excellent energy dissipation capacity of the bolted-cover plate connections. Earthquake action would significantly reduce the ductility of connections. Both diagonal braces and flange reinforcement could dramatically improve the connection's stiffness and bearing capacity, while the flange reinforcement has better hysteretic performance than the diagonal braces reinforcement. The yield energy dissipation of the beam flange contributes most to that of the connection. These experimental studies can provide a reference in the practical design of bolted connections for modular steel buildings.

The construction of implicit Runge–Kutta–Nystrom (RKN) method is considered in this paper. Based on the symmetric, symplectic, and exponentially fitted conditions, a class of implicit RKN integrators is obtained. The new integrators called ISSEFMRKN integrate exactly differential systems whose solutions are linear combinations of functions from the set $\{\exp(\lambda t), \exp(-\lambda t), \lambda\in\mathbb{C}\}$ . In addition, their final stages also preserve the quadratic invariants $\{\exp(2\lambda t), \exp(-2\lambda t)\}$ . Especially, we derived two methods: ISSEFMRKNs1o2 and ISSEFMRKNs2o4 which are of order 2 and 4, respectively. And the method ISSEFMRKNs2o4 has variable nodes. The derived method ISSEFMRKNs2o4 reduces to the classical RKN method (Qin and Zhu in Comput. Math. Appl. 22(9):85–95, 1991) as $\lambda h\rightarrow0$ . The numerical results show that our methods possess the efficiency and competence compared with some implicit RKN methods in the literature. Especially, ISSEFMRKNs2o4 improves the accuracy compared with unmodified method ISSEFRKNs2o4 proposed in (Zhai and Chen in Numer. Algebra Control Optim. 9(1):71–84, 2019).

Splice connection consisting of slip-critical high strength bolt and side plate is a promising connection type for future modular construction. However, recognitions on basic performance for this connection are still limited. To fill this gap, this paper conducted a comprehensive research on basic bending behavior of a simple splice connection proposed by the authors for corner-supported steel modular building. The basic bending behavior of the proposed splice connection was analyzed in details by combined experiments and numerical simulations. It is found that the proposed splice connection can achieve a favorable ductile behavior in bending. Bilinear profile with two stages is clearly observed in the relationship between moment and connection rotation. These two stages have different stiffness but the applied load can keep increasing in the second stage with excessive deformation of the specimen. Such phenomenon reveals adequate reserve of bending resistance for the proposed splice connection under large deformation scenario. Based on method of farthest point, a transition point is defined and determined in the relationship between moment and connection rotation. This transition point represents an important change in the bending behavior, which is valuable for practical design. Numerical simulations are also introduced to supplement the tests. The analyses on stress states of components and variation in bolt pre-tension force properly explains anisotropy in resistance at the transition point for different loading directions. A parametric study is further conducted. Results indicate that the proposed splice connection possesses satisfactory tolerance for loss of bolt pre-tension force in the practical construction.

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007–2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (

While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely. About 60% of these recipient DC displayed donor MHC class I, indicating cross-dressing. By contrast, only a very minor fraction (0–2%) of cross-dressed DC (CD-DC) was evident in the spleen. CD-DC sorted from liver grafts expressed much higher levels of T cell inhibitory programed death ligand 1 (PD-L1) and high levels of IL-10 compared with non CD-DC (nCD-DC) isolated from the graft. Concomitantly, high incidences of programed death protein 1 (PD-1)(hi) T cell immunoglobulin and mucin domain containing-3 (TIM-3)(+) exhausted graft-infiltrating CD8(+) T cells were observed. Importantly, unlike nCD-DC, the CD-DC failed to stimulate proliferation of allogeneic T cells but markedly suppressed anti-donor host T cell proliferation. CD-DC were much less evident in allografts from DNAX-activating protein of 12kDa (DAP12)(−/−) donors that were rejected acutely. CONCLUSION: These findings suggest that graft-infiltrating PD-L1(hi) CD-DC may play a key role in the regulation of alloimmunity and in the induction of liver transplant tolerance.

Liver ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations. Additionally, tissue injury milieu activates PRR-independent receptors which also regulate inflammatory disease processes. Thus, the innate immune mechanism of liver ischemia-reperfusion injury involves diverse molecular and cellular interactions, subjected to both endogenous and exogenous regulation in different cells. A better understanding of these complicated regulatory pathways/network is imperative for us in designing safe and effective therapeutic strategy to ameliorate liver ischemia-reperfusion injury in patients.

Objective To explore the relationships of the expression of miR-145 to the clinicopathological characteristics and prognosis of patients with breast cancer complicated by type 2 diabetes mellitus (T2DM). Methods A total of 257 female patients with breast cancer were enrolled for our experiment, including 140 patients with simple breast cancer (control group) and 117 patients with breast cancer complicated by T2DM (observation group). Patients were treated with modified radical mastectomy supplemented with radiotherapy, chemotherapy and endocrine therapy. qRT-PCR was used for the detection of miR-145 expression in patients of both groups. Follow-up lasted 13-60 months. Results The relative expression of miR-145 in the observation group was significantly lower than that in the control group (pConclusions Loss of miR-145 expression is related to the development of breast cancer complicated by T2DM, and low miR-145 expression might be an adverse prognostic factor in patients with this disease.

BACKGROUND Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. MATERIAL AND METHODS qRT-PCR was used to analyze the expression level of TUG1 and p63 in 75 colon cancer tissues and the matched adjacent non-tumor tissue. In vitro, cultured colon cancer cell lines HCT-116 and LoVo were used as cell models. TUG1 and p63 were silenced via transferring siRNA into HCT-116 or LoVo. The effects of TUG1 were investigated by examining cell proliferation, apoptosis, and migration. RESULTS Among the 75 colon cancer cases, the expression of TUG1 was significantly higher in colon cancer tissues compared with the matched adjacent non-tumor tissue, while p63 expression was lower in the tumor tissue. In HCT-116 and LoVo, the expression of TUG1 was significantly increased by p63 siRNA transfection. Furthermore, down-regulation of TUG1 by siRNA significantly inhibited the cell proliferation and promoted colon cancer cell apoptosis. In addition, inhibition of TUG1 expression significantly blocked the cell migration ability of colon cancer cells. CONCLUSIONS LncRNA TUG1 may serve as a potential oncogene for colon cancer. Overexpressed TUG1 may contribute to promoting cell proliferation and migration in colon cancer cells.

An adjustable slab-aberration compensator (ASAC) with the ability to compensate the large magnitude inherent wavefront aberrations in the slab width direction is proposed and experimentally demonstrated. The ASAC has a size of 130mm×45mm (effective aperture of 75mm×28mm) and 11 actuators along the length with a contact spacing of 8 mm. The design is optimized by simulations in terms of the mirror’s coupling coefficient with the contact areas, mechanical properties of the driving units, and the mirror thickness. The initial surface figure of the ASAC has PV and RMS values of 55 nm and 10 nm, and the dynamic range is 30 µm. In our experiments, a 20 kW Nd: YAG quasi-continuous wave (QCW) slab laser is further compensated by the ASAC system. The beam quality increases from 15× to 3.5× diffraction limit at 20 kW output after correction. Besides, the proposed ASAC can maintain the surface shape after power shutdown and have good thermal stability. The temperature rise of the ASAC is less than 7 °C in the 20 kW laser correction experiment.

Jin-Chen Hu,1,* QuanWang,2,* Li-Xin Jiang,1 Li Cai,3 Hui-Yuan Zhai,1 Zeng-Wu Yao,1 Meng-Lai Zhang,1 Ye Feng4 1Department of Gastrointestinal Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China; 2Department of Gastrointestinal and Anal Surgery, The First Hospital of Jilin University, Changchun, China; 3Department of Pathology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China; 4Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China *These authors contributed equally to this work Objective: In this research, we explored the effect of long non-coding RNA (lncRNA) AOC4P on gastrointestinal stromal tumor (GIST) cells. Materials and methods: The expression of lncRNA AOC4P in tissues was detected by real-time PCR (RT-PCR). The epithelial–mesenchymal transition (EMT)-related proteins in tissues were analyzed by Western blot. The experiment included negative control group (CN), silence AOC4P group (si AOC4P), and silence negative control group (si CT). RT-PCR, MTT, Scratch, Transwell, and Annexin V-FITC methods were used to detect the expression of lncRNA AOC4P, cell proliferation, cell migration ability, cell invasion ability, and apoptosis, respectively. The EMT-related proteins including TGF-β, ZEB1, Vimentin, Snail, and E-cadherin were analyzed by Western blot. Results: The expression of lncRNA AOC4P and the expression of EMT-related proteins in high-risk GISTs were higher than that in low- and intermediate-risk GISTs (P

Background & Aims Glycogen synthase kinase 3β (Gsk3β [ Gsk3b ]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo . Methods We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Results Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro . These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [ Nr0b2 ]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase–Akt signalling pathway. In vivo , myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia–reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK–SHP pathway by liver ischaemia was demonstrated in tumour resection patients. Conclusions Gsk3β promotes innate proinflammatory immune activation by restraining AMPK activation. Lay summary Glycogen synthase kinase 3β promotes macrophage inflammatory activation by inhibiting the immune regulatory signalling of AMP-activated protein kinase and the induction of small heterodimer partner. Therefore, therapeutic targeting of glycogen synthase kinase 3β enhances innate immune regulation and protects liver from ischaemia and reperfusion injury.

Although pretransplant diabetes is a risk factor for mortality post-liver transplant, the underlying mechanism has not been fully defined. In a murine liver partial warm ischemia model, we addressed the question of how diabetes/hyperglycemia impacted tissue inflammatory injuries against ischemia reperfusion (IR), focusing on the advanced glycation endproduct (AGE) and its receptor (RAGE) pathway. Our results showed that hepatocellular injury was exacerbated in streptozotocin-induced diabetic mice against IR, in association with hyper-inflammatory immune activation in livers. Serum levels of AGEs, but not HMGB1, were increased in diabetic mice in response to liver IR. Both RAGE antagonist peptides and small interfering RNA alleviated liver injuries and inhibited inflammatory immune activation against IR in diabetic, but not normal, mice. Kupffer cells (KCs)/macrophages, but not hepatocytes, from diabetic mice expressed significantly higher levels of RAGE, leading to their hyper-inflammatory responsiveness to both TLR ligands and AGEs. In vitro, hyperglycemia increased macrophage RAGE expression and enhanced their TLR responses. Our results demonstrated that activation of the AGE-RAGE signaling pathway in KCs was responsible for hyper-inflammatory immune responses and exacerbated hepatocellular injuries in diabetic/hyperglycemic hosts against liver IR.

BackgroundAlthough rapamycin (RPM) have been studied extensively in ischemia models, its functional mechanisms remains to be defined.MethodsWe determined how RPM impacted the pathogenesis of ischemia-reperfusion injury (IRI) in a murine liver partial warm ischemia model, with emphasis on its regulation of hepatocyte death.ResultsRapamycin protected livers from IRI in the presence of fully developed liver inflammatory immune response. Rapamycin enhanced liver autophagy induction at the reperfusion stage. Dual mammalian (mechanistic) target of rapamycin (mTOR)1/2 inhibitor Torin 1, despite its ability to induced autophagy, failed to protect livers from IRI. The treatment with RPM, but not Torin 1, resulted in the enhanced activation of the mTORC2-Akt signaling pathway activation in livers after reperfusion. Inactivation of Akt by Triciribine abolished the liver protective effect of RPM. The differential cytoprotective effect of RPM and Torin 1 was confirmed in vitro in hepatocyte cultures. Rapamycin, but not Trin 1, protected hepatocytes from stress and tumor necrosis factor-α induced cell death; and inhibition of autophagy by chloroquine or Akt by Triciribine abolished RPM-mediated cytoprotection.ConclusionRapamycin protected livers from IRI by both autophagy and mTORC2-Akt activation mechanisms.