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Inducing cancer differentiation is a promising approach to treat cancer. Here, we identified chlorogenic acid (CA), a potential differentiation inducer, for cancer therapy, and elucidated the molecular mechanisms underlying its differentiation-inducing effects on cancer cells. Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expression was analyzed by microarray analysis, qRT-PCR, and protein measurement, and molecular biology techniques were employed for mechanistic studies. LC/MS analysis was the method of choice for chemical detection. Finally, the anticancer effect of CA was evaluated both and Results: Cancer cells treated with CA showed reduced proliferation rate, migration/invasion ability, and mitochondrial ATP production. Treating cancer cells with CA resulted in elevated SUMO1 expression through acting on its 3'UTR and stabilizing the mRNA. The increased SUMO1 caused c-Myc sumoylation, miR-17 family downregulation, and p21 upregulation leading to G /G arrest and maturation phenotype. CA altered the expression of differentiation-related genes in cancer cells but not in normal cells. It inhibited hepatoma and lung cancer growth in tumor-bearing mice and prevented new tumor development in naïve mice. In glioma cells, CA increased expression of specific differentiation biomarkers Tuj1 and GFAP inducing differentiation and reducing sphere formation. The therapeutic efficacy of CA in glioma cells was comparable to that of temozolomide. CA was detectable both in the blood and brain when administered intraperitoneally in animals. Most importantly, CA was safe even at very high doses. CA might be a safe and effective differentiation-inducer for cancer therapy. \"Educating\" cancer cells to differentiate, rather than killing them, could be a novel therapeutic strategy for cancer.

Background：Overexpression of G-protein coupled receptor 34 （GPR34） affects the progression and prognosis of human gastric adenocarcinoma,however,the role of GPR34 in gastric cancer development and progression has not been well-determined.The current study aimed to investigate the effect of GPR34 knockdown on the proliferation,migration,and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms.Methods：The expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting.HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study.Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA （ShRNA） on the expression of GPR34 in HGC-27 gastric cells.The proliferation,migration of these cells were examined by Cell Counting Kit-8 and transwell.We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting.Results：The ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34,and significantly down-regulated the expression of PIK3CB （P ＜ 0.01）,PIK3CD （P ＜ 0.01）,PDK1 （P ＜ 0.01）,phosphorylation of PDK1 （P ＜ 0.01）,Akt （P ＜ 0.01）,and ERK （P ＜ 0.01）.Furthermore,GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity （P ＜ 0.01）.Conclusions：GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer.

Aiming to solve the problems of the low electrolyte flow rate at leading edge and trailing edge and poor uniformity of the end clearance flow field during the electrochemical machining (ECM) of diffuser blades, a gap flow field simulation model was established by designing three liquid-increasing channels at the leading edge and the trailing edge of the cathode. The simulation results indicate that the liquid-increasing hole channel (LIHC) with an outlet area S of 1.5 mm 2 and a distance L from channel center to edge point of 3.2 mm achieves optimal performance. In addition, the experiment results show that the optimized cathode with liquid-increasing hole channel (LIHC) significantly improves the machining efficiency, accuracy, and surface quality. Specifically, the feed speed increased from 0.25 mm/min to 0.43 mm/min, the taper decreased from 4.02° to 2.45°, the surface roughness value of the blade back reduced from 1.146 to 0.802 µm. Moreover, the roughness of the blade basin decreased from 0.961 to 0.708 µm, and the roughness of the hub reduced from 0.179 to 0.119 µm. The results prove the effectiveness of the proposed method and can be used for ECM of other complex structures with poor flow field uniformity.

A proline-rich region was found in Streptococcus mutans ( S. mutans ) surface antigen I/II (Ag I/II). The functions of this region were explored to determine its role in the cariogenic abilities of S. mutans ; specifically, the proline-rich region was compared with human amelogenin. The full-length amelogenin genes were cloned from human (AmH) and surface antigen I/II genes from S. mutans . Then, the genes expressed and purified. We analyzed the structure and self-assembly ability of AmH and Ag I/II, compared their capacities to induce mineralization, and assessed the adhesion ability of S. mutans to AmH- and Ag I/II-coated tooth slices. AmH formed ordered chains and net frames in the early stage of protein self-assembly, while Ag I/II formed irregular and overlapping structures. AmH induced mineralization possessed a parallel rosary structure, while Ag I/II-induced mineralization is rougher and more irregular. The S. mutans adhesion assay indicated that the adhesion ability S. mutans on the Ag I/II-induced crystal layer was significantly higher than that on the AmH-induced crystal layer. S. mutans’ Ag I/II may have evolved to resemble human amelogenin and form a rougher crystal layer on teeth, which play a competitive mineralization role and promotes better bacterial adhesion and colonization. Thus, the cariogenic ability of S. mutans Ag I/II is increased.

Background The tissue healing after autologous tooth transplantation primarily relies on the physiological stimulation of the periodontal ligament to promote the reparative formation of cementum and alveolar bone. Previous studies have demonstrated the role of amelogenin (AMG) in periodontal repair and regeneration, but research on its effect in autotransplanted teeth remains limited. Objective To investigate the effects of AMG on hPDLSCs derived from isolated teeth in vitro and to evaluate its potential to enhance periodontal and bone reconstruction following tooth transplantation in vivo. Methods Sixteen teeth from two beagles were divided into AMG-treated and control groups ( n  = 8 each). Retention rate, mobility, probing depth, and radiographic healing were assessed postoperatively. At 6 months, micro-CT, H&E, Masson’s trichrome, and TRAP staining evaluated bone reconstruction and root resorption. hPDLSCs were cultured with or without AMG, and viability, proliferation, migration (Calcein AM/PI, CCK-8, scratch assay), and osteogenic differentiation (ALP, Alizarin Red S, RT-qPCR, Western blot) were analyzed. Results In vitro assays demonstrated that AMG significantly promoted the proliferation and migration of hPDLSCs. Under osteogenic differentiation conditions, AMG-treated hPDLSCs exhibited upregulated mRNA levels of ALP, OPN, TGF-β1, COL-I, and COL-III, along with enhanced protein expression of BSP, OPN, ALP, COL-I and RUNX2. Increased ALP activity and mineralized nodule formation further confirmed the osteogenic potential of AMG. In vivo experiments revealed that AMG application improved cementum-like tissue repair and reduced root resorption in transplanted teeth. Conclusion These findings highlight that AMG can enhance key regenerative processes in vitro and improve periodontal healing outcomes in a beagles autotransplantation model under the conditions tested, emphasizing its therapeutic potential in optimizing hPDLSCs-mediated tissue repair during tooth transplantation.

The influence of CO2 on the mechanical properties of shale is one of the key factors to consider for enhancing shale oil and gas exploitation and realizing CO2 geological storage. In this paper, triaxial mechanical experiments of rock under real-time contact with CO2 under different conditions were carried out for the Chang 7 shale of the Yanchang Formation in the Ordos Basin. The results show that under the influence of real-time contact with CO2, the triaxial compressive strength of shale decreases with an average decrease of 3.77% and a maximum decrease of 6.58% under the experimental conditions. The elastic modulus increased with an average increase of 8.54% and a maximum increase of 11.95%. The core compression failure presents a small degree of multi-fracture complex failure. With an increase in CO2 exposure time, temperature, and pressure, the triaxial compressive strength gradually decreases, the elastic modulus gradually increases, and the compression failure of shale core is gradually complicated. The variation in mechanical parameters with time, temperature, and pressure under the influence of CO2 real-time contact was quantitatively described. The effect of gaseous CO2 on shale mechanical parameters and core compression failure is significantly weaker than that of supercritical CO2. This research provides theoretical and data support for supercritical CO2-enhanced shale oil and gas recovery and carbon geological storage from a rock mechanics perspective.

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.

Introducing other elements into gallium oxide materials to modify their properties is a hot topic today. This paper attempts to introduce Bi element to prepare (Bi x Ga 1-x ) 2 O 3 alloy semiconductor thin film by radio frequency co-sputtering, so as to achieve precise and effective tuning of its band gap. The sputtering power of Ga 2 O 3 target remains constant at 80 W. The content of Bi element in the material is adjusted by varying the sputtering power of the Bi 2 O 3 target. Samples with different Bi doping concentrations were obtained after annealing at 800 °C for 2 h. Fortunately, (Bi x Ga 1-x ) 2 O 3 semiconductor alloy films were successfully prepared by radio frequency co-sputtering, and the optical energy gap could be adjusted approximately linearly in the range of 5.14 to 5.27 eV by varying the Bi content. X-ray diffraction and scanning electron microscope results show that a phase transition occurs in the material when the sputtering power of Bi 2 O 3 is 40 W. The results of Urbach energy and film transmittance indicate that moderate Bi doping can reduce the disorder of the material structure and improve the transmittance of the film. However, excessive Bi doping introduces more defects, increasing the scattering and absorption of the defects, ultimately leading to a reduction in film transmittance. These findings have propelled research in the field of gallium oxide doping and its band gap modulation.

Based on the fact that aberrant overexpression of some growth factor receptors was observed in a variety of human cancer cells, a novel nonviral gene delivery system GE7, which contains a 16-amino-acid ligand for identifying EGF receptor was constructed for tumor-targeted gene therapy. Intravenous administration of GE7 system revealed that it has the ability to target β-galactosidase ( β-gal ) reporter gene into murine hepatoma (Hepa) cells. Owing to the limited antitumor effects elicited by a single-gene transfer, recent efforts to treat malignancy using combined gene therapy have been accomplished with varying degrees of success. In this study, the human cyclin-dependent kinase inhibitor gene p21 WAF − 1 and the murine cytokine gene granulocyte–macrophage colony-stimulating factor ( GM-CSF ) were used simultaneously for in vivo gene therapy through systemic injection of the EGF R targeted GE7/DNA complex into murine hepatoma-bearing mice. The results demonstrated that combined administration of p21 WAF − 1 and GM-CSF could remarkably inhibit the growth of subcutaneously transplanted hepatoma Hepa cells, and significantly increase the survival rate of tumor-bearing mice. The activities of natural killer (NK) cells and specific cytotoxic T lymphocytes (CTL) were clearly enhanced after combined gene therapy. In vitro experiments showed that p21 WAF − 1 gene transfer exhibited a suppressive function on the growth of Hepa cells and the expression of H-2K b and B7-1 molecules on Hepa cells increased significantly after combined genes delivery. All these results suggested that the GE7 system was able to target therapeutic genes efficiently to cancer cells, which showed high EGF R expression. The cotransfer of p21 WAF − 1 and GM-CSF genes apparently inhibited the growth of tumors through (a) the arrest of tumor cell growth and (b) the enhancement of systemic antitumor immunity.

The network with some or all of characteristics including self-organization, self-similarity, attractor, small world and scale-free is referred to as a complex network. A complex network might demonstrate various uncertainties, such as the unknown node kinetics and the unknown network topology. The network topology identification using the observing output data of the network is a crucial step for complex network analysis, which is of great importance to understand the networks' properties and regulate network. In this paper, the output variable is used to drive the response network to identify partial time-varying topology of the drive network with unknown parameters. The synchronization between the response network and drive network and the successful identification are guaranteed by the Lyapunov stability theorem. The feasibility of the proposed method is demonstrated using two examples. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka. Ovo je primjer sažetka.