Research on laser target dynamic tracking system with rotating polarization grating.

A micromechanical target tracking system based on polarization grating (PG) is designed to meet the conformal design of laser communication systems and to realize the lightweight and miniaturization of space laser communication networking. The rotating dual PGs are applied to the dynamic tracking of laser targets for the first time, the relationship between the target position and the dual polarization gratings (PGs) angles is defined, and the PG beam deflection multi-coordinate construction and decoupling are carried out. A dual PGs mathematical model was established, and a controller based on the dual PGs system loop was designed. After calibration and dynamic verification of the dual PGs, the unmanned aerial vehicle (UAV) tracking experiment is conducted for the first time, and the dual axis closed-loop tracking error of the dynamic target is within 300µrad (RMSE). The feasibility of dual PGs tracking formula, the feasibility of laser target fixed-point closed-loop control, and the dynamic closed-loop tracking performance are verified. In engineering applications, the dual PGs tracking system has guiding significance for realizing the lightweight and miniaturization of system integration, as well as the possibility to replace the traditional tracking control system.

A novel germline frameshift mutation in the MLH1 gene in a patient with Lynch syndrome.

Lynch syndrome (LS) is an autosomal dominant inherited disorder, characterized by a predisposition to various cancers, mainly colorectal cancer (CRC). LS is caused by germline mutations in DNA mismatch repair genes i.e. mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this study, we report a novel germline frameshift mutation in the MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] in a 34-year-old male patient with LS. This MLH1 alteration has never been reported in any database or any publications. The frameshift mutation in MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] was confirmed by Sanger sequencing conducted on peripheral blood of the proband. Meanwhile, Sanger sequencing results revealed the proband's uncle was the carrier. As multiple downstream germline frameshift mutations of this variation are pathogenic, such as MLH1 M35fs, N38fs, and S44fs, it is predicted that MLH1 p.(Glu34ArgfsTer4) might be also pathogenic. Meanwhile, this MLH1 mutation p.(Glu34ArgfsTer4) is predicted to be disease-causing by the MutationTaster software, as the duplication c.99dupA introduced a premature stop codon early in the translation, resulting in a non-functional protein. This study may contribute to the mutational spectrum of MLH1 leading to LS.

A combination of methylation and protein markers is capable of detecting gastric cancer detection by combined markers.

Aim: This study aimed to validate a combination of mSEPT9, mRNF180 and CA724 for gastric cancer (GC) detection. Patients & methods: The performance of mSEPT9, mRNF180 and CA724 was examined in a prospective cohort study with 518 participants (151 with GC, 56 with atrophic gastritis, 87 with other gastrointestinal diseases and 224 with no evidence of disease). Results:mSEPT9, mRNF180 or CA724 alone detected 48.3, 37.1 and 43.1% of GC, respectively. The combination of mSEPT9 and mRNF180 detected 60.3% of GC, and the combination of all three markers detected 68.6% of GC. The detection sensitivity of mSEPT9 and mRNF180 was significantly higher for gastric body and in elder subjects. mSEPT9 was correlated with poorer GC survival. Conclusion: The combination of mSEPT9, mRNF180 and CA724 was adequately sensitive for GC detection. The blood mSEPT9 was predictive for GC prognosis.

Lay abstract Gastric cancer is the most common cancer type in the digestive system. In this study we developed an effective and convenient blood-based test to detect gastric cancer. This test combined a conventional protein test with a newly invented methylation test. We aimed to validate the test and examine its performance using a prospective cohort study. The study showed that the test has promising potential for noninvasive early detection of gastric cancer. We found that single protein or methylation markers detected a proportion of gastric cancer cases, while a combination of these markers exhibited maximal detection capability. Therefore we concluded that the combined test provided adequate efficacy and should be used as a strategy for future gastric cancer detection.

The enhancement of Tetrandrine to gemcitabine-resistant PANC-1 cytochemical sensitivity involves the promotion of PI3K/Akt/mTOR-mediated apoptosis and AMPK-regulated autophagy.

BACKGROUND: In the process of tumor development, the resistance of pancreatic cancer cells to gemcitabine (GEM) is mainly due to the suppression and dysregulation of apoptosis signals to a large extent. Therefore, it is very necessary to develop pro-apoptotic drugs for combined treatment of pancreatic cancer to increase the activity of GEM and improve the prognosis of pancreatic cancer. METHODS AND RESULTS: GEM-resistant PANC-1 cells were treated with increasing doses of GEM. The effects of GEM and TET on apoptosis were evaluated by flow cytometry and Hoechst 33258 staining. We also evaluated the expression of survivin by real-time PCR, and the expression levels of proteins involved in apoptosis, autophagy, and PI3K/Akt/mTOR signaling were detected by western blotting. The results showed that TET downregulated expression of survivin by inhibiting the PI3K/Akt/mTOR signaling pathway to promote pancreatic cancer cell apoptosis, thereby enhancing pancreatic cancer cell sensitivity to GEM. Moreover, TET enhanced cytotoxic and autophagy-dependent cell death by upregulating the AMPK-autophagy axis, and this effect was reversed by inhibition of AMPK. CONCLUSIONS: TET promotes apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway and promotes autophagy via up-regulating the AMPK signaling pathway to play an anti-tumor effect in GEM-resistant pancreatic cancer cells, which represents a new therapeutic strategy for the treatment of GEM-resistant pancreatic cancer.

Controllable linear asymmetric transmission and perfect polarization conversion in a terahertz hybrid metal-graphene metasurface.

We propose a three layered metal-graphene-metal metasurface to investigate the controllable linear asymmetric transmission and perfect polarization conversion in THz regime, by using the finite-difference time-domain (FDTD) method. An on-to-off control of asymmetric transmission and perfect polarization conversion is achieved by changing the Fermi energy of graphene from 0.8 eV to 0 eV. We present the electric field distribution and Fabry-Perot-like cavity model to analyze the working mechanisms. By gradually shifting the Fermi energy of graphene, two functions are realized, i.e., controllable linear asymmetric transmission and controllable total transmission with near perfect polarization conversion.

ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis.

BACKGROUND: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. AIM: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. METHODS: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. RESULTS: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. CONCLUSION: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.

RNA interference­mediated inhibition of survivin and VEGF in pancreatic cancer cells in vitro.

The aim of the present study was to investigate the effects of simultaneous short hairpin RNA (shRNA)­targeted survivin and vascular endothelial growth factor (VEGF) inhibition on the proliferation, apoptosis and angiogenesis of human pancreatic cancer cells (Panc­1). Targeted small interfering RNA (siRNA) expression vectors of survivin and VEGF were constructed and transfected into Panc­1 cells. The downregulation of survivin and VEGF expression was evaluated by real­time PCR and western blot analysis. The effects of targeted shRNA on the proliferation and apoptosis of Panc­1 cells were analyzed by MTT assay and flow cytometry (FCM). The culture medium from Panc­1 cells transfected with siRNA was collected and human umbilical vein endothelial cells (HUVECs) were seeded in this media. The proliferation and apoptosis of the HUVECs were also investigated by MTT assay and FCM. A transfected cell line (Panc­1/survivin­shRNA and Panc­1/VEGF­shRNA) was established in which the expression of survivin and VEGF was downregulated. The cell viabilities of Panc­1 cells and HUVECs in the combined inhibition groups were markedly decreased compared with the controls. The cell apoptosis rates of Panc­1 cells and HUVECs in the combined inhibition groups were observed to be significantly increased compared with the controls. The simultaneous RNA interference­mediated downregulation of survivin and VEGF expression inhibited proliferation and induced the apoptosis of Panc­1 cells and HUVECs, indicating that combined therapy with survivin and VEGF inhibition may serve as a potential strategy for the treatment of pancreatic cancer.

Double inhibition of NF-κB and XIAP via RNAi enhances the sensitivity of pancreatic cancer cells to gemcitabine.

The majority of patients with pancreatic cancer are resistant to gemcitabine. One of the mechanisms involved is the anti-apoptotic ability of these cells. The median lethal dose (LD50) of gemcitabine for PANC-1 cells was higher than that for Mia PaCa-2 cells and the former had higher nuclear factor-κB (NF-κB) and X-linked inhibitor of apoptosis protein (XIAP) levels. NF-κB contributes to the inhibition of apoptosis by the downregulation of downstream genes, such as XIAP and Bcl-2 and it confers chemoresistance. The two cell lines were infected with NF-κB p65 small interfering RNA (siRNA). p65 protein was effectively downregulated accompanied by the downregulation of XIAP protein. The combination treatment with gemcitabine and p65 siRNA increased the apoptotic rates in both cell lines; however, this was not sufficient. XIAP is involved in apoptosis to a greater extent compated to Bcl-2. XIAP may serve as another factor affecting the sufficiency of chemotherapy. XIAP siRNA was designed to knockdown XIAP. Mia PaCa-2 and PANC-1 cells were co-infected with XIAP siRNA and p65 siRNA. XIAP and p65 proteins were effectively downregulated and the gemcitabine-induced apoptotic rates were significantly increased. These results suggest that XIAP and NF-κB are two important factors conferring the chemoresistance of pancreatic cancer cells, and that their downregulation via RNAi effectively enhances the chemosensitivity of pancreatic cancer cells to gemcitabine.

Genetic immune modulation of Ran GTPase against different microbial pathogens.

Septic shock characterized by pro-inflammatory cytokine storm can be induced by a variety of microbial infections. Typical pro-inflammatory cytokines include TNFalpha, IL1 and IL6. Although one or more of them is often expressed in any given microbial infection, usually it is the elevation of one cytokine that becomes predominant at a particular time in a given infection. Here we showed that administration of adenoviral antigens alone led to a predominant elevation of serum IL6 but not TNFalpha Administration of endotoxin together with adenoviral antigens led to elevation of both serum IL6 and TNFalpha. In vivo expression of RanC/d, but not RanT/n or LacZ into peritoneal macrophages rapidly down-modulated the levels of these cytokines in both experimental situations. It also correlated with reduced liver inflammatory damage and increased resistance to septic shock. We conclude that RanC/d can be applied to down-modulating production of cytokines induced by microbial products other than endotoxin and to render resistance to mice against septic shock induced by one or more microbial pathogens. The ability of using RanC/d to down-modulate and RanT/n to up regulate host innate immune response induced by multiple microbial pathogens is illustrated in this study. Incorporation of either or both RanC/d and RanT/n alleles into appropriate vectors will produce genetics vaccines valuable for biodefense and medically important illness in which host immune system against invading agents is severely burdened.