Generating multi-focus beams with a spatial non-uniform coherence structure.

We introduce a class of structured light beams, named multi-focus beams, which exhibit self-focusing at multiple propagation distances. We show that the proposed beams not only have the ability to produce multiple longitudinal focal spots, but also that the number, intensity, and position of the foci can be controlled by adjusting the initial beam parameters. Furthermore, we demonstrate that these beams still exhibit self-focusing in the shadow of an obstacle. We have experimentally generated such beams and the results are consistent with the theoretical predictions. Our studies may find application where fine control of the longitudinal spectral density is needed, such as longitudinal optical trapping and manipulation of multiple particles, and transparent material cutting.

What Happened in the Hippocampal Axon in a Rat Model of Posttraumatic Stress Disorder.

Studies from postmortem and animal models have revealed altered synapse morphology and function in the brain of posttraumatic stress disorder (PTSD). And the effects of PTSD on dendrites and spines have been reported, however, the effection on axon include microtubule (MT) and synaptic vesicles of presynaptic elements remains unknown. Hippocampus is involved in abnormal memory in PTSD. In the present study, we used the single prolonged stress (SPS) model to mimic PTSD. Quantitative real-time polymerase chain reaction (RT-qPCR) and high-throughput sequencing (GSE153081) were utilized to analyze differentially expressed genes (DEGs) in the hippocampus of control and SPS rats. Immunofluorescence and western blotting were performed to examine change in axon-related proteins. Synaptic function was evaluated by measuring miniature excitatory postsynaptic currents (mEPSCs). RNA-sequencing analysis revealed 230 significantly DEGs between the control and SPS groups. Gene Ontology analysis revealed upregulation in axonemal assembly, MT formation, or movement, but downregulation in axon initial segment and synaptic vesicles fusion in the hippocampus of SPS rats. Increased expression in tau, ß-tubulin MAP1B, KIF9, CCDC40, DNAH12 and decreased expression in p-tau, stathmin suggested SPS induced axon extension. Increased protein expression in VAMP, STX1A, Munc18-1 and decreased expression in synaptotagmin-1 suggested SPS induced more SNARE complex formation but decreased ability in synaptic vesicle fusion to presynaptic active zone membrane in the hippocampus of SPS rats. Further, low mEPSC frequency in SPS rats indicated dysfunction in presynaptic membrane. These results suggest that axon extension and synaptic vesicles fusion abnormality are involved in dysfunction of PTSD.

Key Mechanisms and Potential Targets of the NLRP3 Inflammasome in Neurodegenerative Diseases.

Neurodegenerative diseases are neuronal disorders characterized by the loss of a large number of neurons in the human brain. Innate immunity-mediated neuroinflammation actively contributes to the onset and progression of neurodegenerative diseases. Inflammasomes are involved in the progression of the innate immune response and are responsible for the maturation of caspase-1 and inflammatory cytokines during neuroinflammation. The nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome, which is one of the most intensively investigated inflammasomes, has been reported to play a key role in neurodegenerative diseases. Here, we reviewed the mechanisms, role, and latest developments regarding the NLRP3 inflammasome with respect to three neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Patient and animal model studies have found that abnormal protein aggregation of Aß, synuclein, or copper-zinc superoxide dismutase-1 (SOD1), which are the main proteins expressed in the three diseases, respectively, can activate microglial cells, induce increased interleukin-1ß (IL-1ß) release, and activate the NLRP3 pathway, leading to neurodegeneration. In contrast, a deficiency of the components of the NLRP3 pathway may inhibit Aß, synuclein, or SOD1-induced microglial activation. These studies indicate a positive correlation between NLRP3 levels and abnormal protein aggregation. However, in the case of ALS, not only microglia but also astrocytes express increased NLRP3 levels and contribute to activation of the NLRP3 pathway. In addition, in this review article, we also focus on the therapeutic implications of targeting novel inhibitors of the NLRP3 inflammasome or of novel drugs that mediate the NLRP3 pathway, which could play a role via NLRP3 in the treatment of neurodegenerative diseases.

MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer.

Gastric cancer is one of the most common types of carcinoma with a threat to global health. MicroRNA-760 (miR-760) was significantly down-regulated in the primary tumour of patients with advanced gastric cancer. However, the role of miR-760 in gastric cancer is still unclear. Herein, miR-760 was down-regulated in gastric cancer tissues. Moreover, miR-760 overexpression and knockdown were conducted in gastric cancer cells (MGC-803 and SGC-7901) in vitro. The in vitro functional assays proved that miR-760 overexpression reduced cell viability, cell cycle, migration and invasion, promoted apoptosis and suppressed MMP activity in MGC-803 cells. Conversely, miR-760 knockdown led to the opposite in SGC-7901 cells. Notably, bone marrow stromal antigen 2 (BST2) was verified as a target gene of miR-760. MiR-760 mimics down-regulated BST2 level in gastric cancer tissues and in MGC-803 cells, whereas miR-760 inhibitor up-regulated its level in SGC-7901 cells. MiR-760-regulated cell properties through reduction of BST2. In addition, miR-760 inhibited tumourigenesis in a nude mouse xenograft model in vivo. In conclusion, our results demonstrated that miR-760 exhibited a suppressive role in gastric cancer via inhibiting BST2, indicating that miR-760/BST2 axis may provide promising therapeutic target for gastric cancer.

Correlation of Intestinal Mucosal Healing and Tight Junction Protein Expression in Ulcerative Colitis Patients.

BACKGROUND: The aim of this study was to investigate the relationship between intestinal mucosal healing and tight junction (TJ) protein expression in patients with ulcerative colitis (UC). MATERIALS AND METHODS: A total of 40 patients with UC were included as an experimental group and UC disease activity was evaluated using the Mayo clinic score (MCS) and 8 patients with normal distal colon served as the control group. The expression of TJ proteins including occludin, ZO-1 and claudin-2 were determined by immunohistochemistry and their correlation with clinical characteristics were also analyzed. RESULTS: Statistically significant differences regarding the MCS and Mayo endoscopic subscore (MES) were observed in both groups (P < 0.01). The Geboes index was significantly increased in patients with active UC compared to patients with quiescent UC and normal controls (P < 0.01). Patients with active and quiescent UC had upregulated expression of claudin-2 and reduced expression of occludin and ZO-1 compared to those of normal controls. The expression of ZO-1 was significantly higher in patients with quiescent UC with mucosa healing (P < 0.05) compared with those without mucosal healing. The expression of ZO-1 and occludin was negatively correlated with MCS, MES, Geboes, C-reaction protein and erythrocyte sedimentation rate. The expression of claudin-2 was positively correlated with MCS, MES, Geboes, C-reaction protein and erythrocyte sedimentation rate. CONCLUSIONS: These findings suggest that TJ proteins play a crucial role in mucosal healing, and may be a potential marker of response when evaluating therapeutic interventions.

BST2 promotes cell proliferation, migration and induces NF-κB activation in gastric cancer.

OBJECTIVES: To investigate the functional roles of bone marrow stromal cell antigen 2 (BST2) in gastric cancer (GC) cells and its implications in the development of GC patients. RESULTS: BST2 was frequently overexpressed in GC tissues compared with the adjacent non-tumorous tissues, and high BST2 expression was correlated with tumor stage and lymphatic metastasis. Furthermore, in vitro experiments demonstrated that knockdown of BST2 by siRNA inhibited cell proliferation, induced apoptosis and repressed cell motility in GC cells. In addition, the pro-tumor function of BST2 in GC was mediated partly through the NF-κB signaling. CONCLUSION: BST2 possesses the oncogenic potential in GC by regulating the proliferation, apoptosis, and migratory ability of GC cells, thereby BST2 could be a potential therapeutic target for the treatment of GC.

NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-ß1/SMADs Pathway.

BACKGROUND AND AIMS: This study aimed to evaluate the antifibrotic effects of NF-E2-Related Factor 2 (Nrf2) on intestinal fibrosis. Intestinal fibrosis is a common complication of Crohn's disease; however, its mechanism of intestinal fibrosis is largely unclear. METHODS: BALB/c mice received 2,4,6-trinitrobenzene sulfonic acid weekly via intrarectal injections to induce chronic fibrotic colitis. They also diet containing received 1% (w/w) tert-butylhydroquinone (tBHQ), which is an agonist of Nrf2. Human intestinal fibroblasts (CCD-18Co cells) were pretreated with tBHQ or si-Nrf2 followed by stimulation with transforming growth factor-ß1 (TGF-ß1), which transformed the cells into myofibroblasts. The main fibrosis markers such as α-smooth muscle actin, collagen I, tissue inhibitor of metalloproteinase-1, and TGF-ß1/SMADs signaling pathway were detected by quantitative real-time RT-PCR, immunohistochemical analysis, and Western blot analysis. Levels of cellular reactive oxygen species (ROS) were detected by dichlorodihydrofluorescein diacetate. RESULTS: tBHQ suppressed the intestinal fibrosis through the TGF-ß1/SMADs signaling pathway in TNBS-induced colitis and CCD-18Co cells. Moreover, Nrf2 knockdown enhanced the TGF-ß1-induced differentiation of CCD-18Co cells. ROS significantly increased in TGF-ß1-stimulated CCD-18Co cells. Pretreatment with H2O2, the primary component of ROS, was demonstrated to block the effect of tBHQ on reducing the expression of TGF-ß1. Moreover, scavenging ROS by N-acetyl cysteine could inhibit the increasing expression of TGF-ß1 promoted by Nrf2 knockdown. CONCLUSIONS: The results suggested that Nrf2 suppressed intestinal fibrosis by inhibiting ROS/TGF-ß1/SMADs pathway in vivo and in vitro.