M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by ß-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of ß-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Effect of transcutaneous electrical acupoint stimulation on postoperative cognitive function in older patients with lung cancer: A randomized, double-blind, placebo-controlled trial.

Objective: This trial was to examine the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive function in older patients who underwent thoracoscopic pulmonary resection. Methods: This was a prospective, randomized, double-blind, placebo-controlled study. 128 patients scheduled for surgery were randomly assigned to the TEAS group and sham-TEAS group. A standardized intervention of TEAS or sham-TEAS on the acupoints of Baihui (DU20) and bilateral Neiguan (PC6), Hegu (LI4), and Zusanli (ST36) from 30 min before anesthesia induction until the end of the surgery, combined with a general anesthetic protocol performed in the two groups respectively. The primary outcome was the incidence of postoperative cognitive dysfunction (POCD) assessed via the Montreal Cognitive Assessment (MoCA) scale at each time point. The secondary outcomes included the results of the Mini-Mental State Examination (MMSE) score, the Numerical Rating Scale (NRS) on pain and sleep, the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30), and a chronic pain questionnaire at relative time points. Results: Participants who completed the 12-month trial of the two groups were well-matched in baseline demographic and clinical parameters. At postoperative day 1, day 7, and day 30 time points, the incidence of POCD in the sham-TEAS group was always significantly higher than in the TEAS group (65.4% vs 20%, 43.6% vs 7.3%, 40% vs 3.6%, all P < 0.001). Also, the TEAS group showed better scores of MMSE, sleep, and pain compared with the sham-TEAS group (all P < 0.001). At 6 and 12 months points, the global health scores of the TEAS group were still significantly higher than the sham-TEAS group, and the prevalence of chronic pain was significantly lower than the sham-TEAS group (all P < 0.05). Conclusion: TEAS could effectively improve the postoperative cognitive function and long-term life quality of geriatric patients with lung cancer.

SALL4 promotes angiogenesis in gastric cancer by regulating VEGF expression and targeting SALL4/VEGF pathway inhibits cancer progression.

BACKGROUND: Spalt-like protein 4 (SALL4) is a stemness-related transcription factor whose abnormal re-expression contributes to cancer initiation and progression. However, the role of SALL4 in cancer angiogenesis remains unknown. METHODS: Analyses of clinical specimens via TCGA datasets were performed to determine the expression level and clinical significance of SALL4 in STAD (Stomach Adenocarcinoma). SALL4 knockdown, knockout, and overexpression were achieved by siRNA, CRISPR/Cas9, and plasmid transfection. The effects of conditioned medium (CM) from SALL4 knockdown or overexpression of gastric cancer cells on endothelial cell proliferation, migration, and tube formation were investigated by CCK-8 assay, transwell migration assay, and tube formation assay. The regulation of VEGF gene expression by SALL4 was studied by qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assay, and electrophoretic mobility shift assay (EMSA). Engineered exosomes from 293T cells loaded with si-SALL4-B and thalidomide were produced to test their therapeutic effect on gastric cancer progression. RESULTS: SALL4 expression was increased in STAD and positively correlated with tumor progression and poor prognosis. SALL4-B knockdown or knockout decreased while over-expression increased the promotion of human umbilical vein endothelial cells (HUVEC) cell proliferation, migration, and tube formation by gastric cancer cell-derived CM. Further investigation revealed a widespread association of SALL4 with angiogenic gene transcription through the TCGA datasets. Additionally, SALL4-B knockdown reduced, while over-expression enhanced the expression levels of VEGF-A, B, and C genes. The results of ChIP and EMSA assays indicated that SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription, which may be associated with increased histone H3-K79 and H3-K4 modifications in their promoter regions. Furthermore, si-SALL4-B and thalidomide-loaded exosomes could be efficiently uptaken by gastric cancer cells and significantly reduced SALL4-B and Vascular Endothelial Growth Factor (VEGF) expression levels in gastric cancer cells, thus inhibiting the pro-angiogenic role of their derived CM. CONCLUSION: These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression. Co-delivery of the functional siRNA and anticancer drug via exosomes represents a useful approach to inhibiting cancer angiogenesis by targeting SALL4/VEGF pathway.

The new advance of SALL4 in cancer: Function, regulation, and implication.

SALL4 (split-like protein 4) is a member of the mammalian homologs of the Drosophila homoeotic gene spalt (sal) and acts as a zinc finger transcription factor to govern the self-renewal and pluripotency of embryonic stem cells. SALL4 expression gradually decreases during development and is even absent in most adult tissues. However, increasing evidence suggests that SALL4 expression is restored in human cancers and its aberrant expression is associated with the progression of many hematopoietic malignancies and solid tumors. The potent roles of SALL4 in regulating cancer cell proliferation, apoptosis, metastasis, and drug resistance have been reported. SALL4 plays a dual role in epigenetic modulation by acting as either an activator or a repressor of its target genes. Furthermore, SALL4 interacts with other partners to control the expression of many downstream genes and the activation of various key signaling transduction pathways. SALL4 is considered as a promising diagnostic and prognostic biomarker and therapeutic target for cancer. In this review, we highlighted the major advances in the roles and mechanisms of SALL4 in cancer and the therapeutic strategies for targeting SALL4 to treat cancer.

The effect of nursing intervention combined with PD-1 inhibitor on platelets, white blood cells, tumor markers and quality of life in patients with lung cancer.

Tumor immunotherapy has become one of the important directions in the field of anti-tumor research. Among them, programmed death molecule-1 (PD-1) and its ligand (PD-L1) inhibitors have attracted considerable attention. This study analyzed the application effects of PD-1 inhibitors assisted nursing intervention in patients with lung cancer (LC). Sixty-eight patients with LC were divided into research group and control group randomly. Control group was treated with PD-1 inhibitor chemotherapy. Research group was treated with PD-1 inhibitors as auxiliary nursing intervention. Platelets, immune function indexes, tumor markers, and white blood cells were analyzed. Clinical efficacy was evaluated by traditional Chinese medicine (TCM) symptom score, survival quality of karnofsky performance scale (KPS) score, living quality of quality of life (QOL) score, and nausea and vomiting classification. Hemoglobin (HB), platelet (PLT) and serum white blood cells (WBC) levels in the two groups were decreased after treatment. HB, PLT and WBC levels were enhanced in research group versus control group. Moreover, carcino-embryonic antigen (CEA), carbohydrate antigen 199 (CA199) and CA125 levels in both groups were reduced after treatment. Compared with before treatment, the levels of cluster of differentiation (CD)3+, CD4+, CD4+/CD8+ in control group and the research group increased, while the CD8+ content was significantly decreased after treatment. And their content of the research group was significantly higher/lower than that of the control group. TCM symptom score, KPS score, QOL score and nausea and vomiting classification were improved in research group compared to control group. PD-1 inhibitors assisted nursing intervention can improve the living quality of patients with LC after chemotherapy.

BASP1 promotes high glucose-induced endothelial apoptosis in diabetes via activation of EGFR signaling.

AIMS: Diabetes mellitus is a common chronic disease of glucose metabolism. Endothelial dysfunction is an early event in diabetes complicated by cardiovascular disease. This study aimed to reveal the expression of BASP1 and its biological roles in endothelial cell dysfunction in diabetes complicated by cardiovascular disease. MATERIALS AND METHODS: By analyzing the databases related to diabetes complicated with coronary heart disease, BASP1 was screened out as an upregulated gene. Human umbilical vein endothelial cells (HUVECs) and primary mouse aortic endothelial cells were treated with high glucose to establish cell models of diabetes-related endothelial dysfunction, and the expression changes of BASP1 were verified by RT-qPCR, western blot, and immunofluorescence. BASP1 was silenced or overexpressed by siRNA or overexpression plasmid, and its effects on cell migration, apoptosis, tube formation, inflammatory response, and ROS were detected. The possible signaling pathway of BASP1 was found and the mechanism of BASP1 on promoting the progression of endothelial dysfunction was explored using the EGFR inhibitor, gefitinib. RESULTS: Bioinformatics analysis indicated that the expression of BASP1 in patients with diabetes mellitus and concomitant coronary heart disease was increased. High glucose induced the upregulation of BASP1 expression in endothelial cells, and showed a time-dependent relationship. Silencing of BASP1 alleviated the damage of high glucose to endothelial cells. BASP1 regulated EGFR positively. The promoting effect of BASP1 on endothelial cell apoptosis may be achieved by regulating the EGFR pathway. CONCLUSION: BASP1 promotes endothelial cell injury induced by high glucose in patients with diabetes, which may be activated by activating the EGFR pathway.

Phase-unwrapping-free 3D reconstruction in structured light field system based on varied auxiliary point.

Three-dimensional (3D) reconstruction is an essential task in structured light field (SLF) related techniques and applications. This paper presents a new method to reconstruct a 3D object point by using many auxiliary points adjacent to it. The relationship between two points in a SLF system is derived. Different from conventional "direct" methods that reconstruct 3D coordinates of the object point by using phase, slope, disparity etc., the proposed method is an "indirect" method as the 3D coordinates of auxiliary points are not needed. Based on the auxiliary point theory, the wrapped phase obtained by 4-step phase-shifting method is sufficient for 3D reconstruction, without the need for phase unwrapping. To the best of our knowledge, this is the first strategy that combines the intrinsic characteristics of structured light and light field for phase-unwrapping-free 3D reconstruction. This paper also analyzes the constraints between system architecture parameters and phase rectification, phase to depth ratio, and presents a relatively simple criterion to guide the system design. Experimental results show that, with an appropriate system architecture, the proposed method can realize accurate, unambiguous, and reliable 3D reconstruction without phase unwrapping.

Waves Propagating in Nano-Layered Phononic Crystals with Flexoelectricity, Microstructure, and Micro-Inertia Effects.

The miniaturization of electronic devices is an important trend in the development of modern microelectronics information technology. However, when the size of the component or the material is reduced to the micro/nano scale, some size-dependent effects have to be taken into account. In this paper, the wave propagation in nano phononic crystals is investigated, which may have a potential application in the development of acoustic wave devices in the nanoscale. Based on the electric Gibbs free energy variational principle for nanosized dielectrics, a theoretical framework describing the size-dependent phenomenon was built, and the governing equation as well as the dispersion relation derived; the flexoelectric effect, microstructure, and micro-inertia effects are taken into consideration. To uncover the influence of these three size-dependent effects on the width and midfrequency of the band gaps of the waves propagating in periodically layered structures, some related numerical examples were shown. Comparing the present results with the results obtained with the classical elastic theory, we find that the coupled effects of flexoelectricity, microstructure, and micro-inertia have a significant or even dominant influence on the waves propagating in phononic crystals in the nanoscale. With increase in the size of the phononic crystal, the size effects gradually disappear and the corresponding dispersion curves approach the dispersion curves obtained with the conventional elastic theory, which verify the results obtained in this paper. Thus, when we study the waves propagating in phononic crystals in the micro/nano scale, the flexoelectric, microstructure, and micro-inertia effects should be considered.

The Efficacy of Tripterygium Glycosides Combined with LMWH in Treatment of HSPN in Children.

OBJECTIVE: This study aimed to explore the clinical efficacy and relevant mechanism of Tripterygium glycosides combined with low molecular weight heparin calcium (LMWH) in the treatment of Henoch-Schönlein purpura nephritis (HSPN) in children. METHODS: 64 cases of children patients with HSPN treated at Qilu Hospital (Qingdao) from January 2015 to May 2020 were selected and randomly divided into the control group and the observation group and 32 cases in each group. Conventional medical treatment was applied in the two groups, besides which the control group was given LMWH while the observation group was given Tripterygium glycosides based on the control group. The clinical efficacy and the indexes of clinical symptoms of the two groups were compared. Immune globulin level, fibrinogen content (FIB), prothrombin time (PT), platelet level (PLT), and activated partial thromboplastin time (APTT) level of the two groups were compared before and after the treatment. RESULTS: The total effective rate in the observation group was significantly higher than that of the control group, and the recurrence rate in the observation group was lower than that in the control group. After treatment, urine red blood cell count and 24 h urine protein were obviously better than those of the control group. There was no statistically significant difference in PT between the two groups of children before and after treatment. The levels of PLT and FIB in the two groups of patients after treatment were significantly lower than before treatment, and the PLT levels in the observation group were lower than those in the control group. CONCLUSION: The combination of Tripterygium glycosides and LMWH had good clinical effects in the treatment of children with HSPN, and it could improve the clinical symptoms, the mechanism of which might be related to the increase of PT, a decrease of PLT, and the improvement of coagulation function.

Upregulation of SIX4 indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma.

BACKGROUND: The role of sine oculis homeobox 4 (SIX4) has been found in some malignant tumors. However, there have been few studies on the function of SIX4 in esophageal squamous cell carcinoma (ESCC). This study aimed to explore the regulatory mechanism of SIX4 in ESCC. METHODS: RT-qPCR and Western blot analysis were used to measure mRNA and protein expression. The function of SIX4 was investigated using CCK-8, colony formation, flow cytometry, wound healing and transwell assays. A mouse xenograft tumor assay was designed to perform in vivo experiments. RESULTS: SIX4 was upregulated in ESCC and indicated poor clinical outcomes in ESCC patients. Functionally, knockdown of SIX4 inhibited cell proliferation and induced apoptosis in ESCC. In addition, the silencing of SIX4 inhibited cell migration, invasion and EMT in ESCC. More importantly, upregulation of SIX4 could activate the PI3K/AKT pathway in ESCC cells and promote tumor growth in vivo. CONCLUSIONS: Upregulation of SIX4 indicates poor clinical outcomes in ESCC patients and promotes tumor growth and cell metastasis in ESCC.

Angiopoietin-like protein 7 mediates TNF-α-induced adhesion and oxidative stress in human umbilical vein epithelial cell.

Tumor necrosis factor-α (TNF-α) promotes monocyte adhesion to endothelium and accumulation of endothelium will lead to atherosclerosis. The present study explored Angiopoietin-like protein (Angptl7) as a potential target in the process of atherosclerosis, and its role in the adhesion and oxidative stress induced by TNF-α in human umbilical vein epithelial cells (HUVEC). The initiation of atherosclerosis is endothelial injury. Angptl7 was dramatically increased in TNF-α-induced HUVEC compared to the control cells. After Angptl7 effectively knocked-down in TNF-α-induced HUVEC, the levels of reactive oxygen species (ROS), interleukin (IL)-1ß, IL-6 and cyclooxygenase-2 (Cox-2) were prominently decreased, whereas the levels of nitric oxide (NO) and endothelia nitric oxide synthase (eNOS) were increased. Inhibition of Angptl7 significantly reversed TNF-α-induced cell adhesion in HUVEC. Finally, downregulation of Angptl7 significantly reduced the expression of nuclear factor-κB (NF-κB) and enhanced the levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) in TNF-α-treated HUVEC. Angptl7 conducted TNF-α-induced oxidative stress and cell adhesion in HUVEC. Therefore, Angptl7 might participate in the development of endothelial injury and further atherosclerosis. This might give us a new insight for investigation of procession of atherosclerosis.

The effect of cubic material nonlinearity on the propagation of torsional wave modes in a pipe.

The effect of cubic material nonlinearity on the propagation in a pipe of the lowest axially symmetric torsional wave mode has been investigated in this paper. Two cases, one that the material of the whole pipe is nonlinear, and the second that a small segment of the pipe is nonlinear, have been considered. For the first case, a first and a third harmonic have been obtained by the perturbation method. Analytical expressions for the two cumulative harmonics have been derived. The second case leads to a scattering problem. The segment produces nonlinear terms in the equation of motion, which can be regarded as a distribution of body forces. The problem is then reduced to a linear scattering problem. An analytical expression for the backscattered wave can be easily obtained by using the elastodynamic reciprocity theorem. Due to the low amplitude of the backscattered wave, the authors propose to add another higher frequency wave to the primary wave, to increase the total magnitude of the scattered wave. An example that the originally scattered wave is amplified 50 times by selecting proper frequencies is presented. Both cases considered here have a potential application to determine the material properties in a region of nonlinear material behavior.

Application performance of a new coagulant in wastewater reuse.

Ultraviolet (UV) absorption characteristics of poly-Al-Zn-Fe (PAZF), a polymerized coagulant containing three kinds of metallic elements prepared from a galvanized-aluminum slag, was analyzed by UV-visible spectrophotometry during its polymerization process. Pollutant removal by PAZF in treating various wastewaters was investigated, in comparison with that of polyaluminum chloride (PAC). The results showed that PAZF can be applied to different wastewaters and had excellent coagulation behavior due to its special internal composition. Various complicated substances having different absorption wavelengths and polymeric properties were produced during the PAZF polymerization process, and the structures of these complicated substances were adjusted continuously with the increasing of the polymerization time. PAZF posed better turbidity and organic matter (chemical oxygen demand, COD(Cr)) removal than PAC for different wastewaters, and the required dosage of PAZF was far lower than that of PAC when achieving the same coagulation performance. For pharmaceutical, sugar, dyeing, simulated pesticide and landscape wastewaters, PAZF gave higher removal of turbidity or COD(Cr) than PAC, by up to 79.5% (coagulant dose: 74 mg/L) or 16% (148 mg/L), 13.4% (111 mg/L) or 10% (185 mg/L), 26.5% (148 mg/L) or 8.1% (18.5 mg/L), 40% (18.5 mg/L) or 13.4% (111 mg/L), and 5% (70 mg/L) or 5% (70 mg/L), respectively.