[Integrin α5 promotes the proliferation, invasion and adhesion of gastric cancer by regulating the FAK/Src/Rac1 signaling pathway].

Objective: To elucidate the biological role and potential mechanism of integrin α5 (ITGA5) in gastric cancer (GC). Methods: From January 2019 to December 2020, 35 pairs of GC tissue [21 males and 14 females, aged (53.8±5.4) years] and matched adjacent tissue samples were collected from GC patients who underwent surgical resection in Zhejiang Provincial People's Hospital. GC and normal gastric mucosa cells were purchased from Beijing Biobw Biotech Company. Quantitative real-time PCR (qRT-PCR), immunohistochemistry, Western blotting were performed to detect the mRNA and protein expression levels of ITGA5, cell adhesion-related genes (pFAK, pSrc, aRac1) in GC cells. Cell Counting Kit-8 (CCK-8), Transwell invasion, wound healing and cell adhesion assays were conducted for GC cell phenotype detection. Results: ITGA5 was highly expressed in GC compared with normal gastric mucosa cells (relative expression increased from 1.00±0.26 to 1.23±0.27,P<0.05). In addition, ITGA5 overexpression promoted the cell proliferation [from (1.14±0.14) OD to (1.61±0.14) OD], migration ability [from (20.3±2.3)% to (56.4±6.1)%], invasion ability (from 144.0±4.6 to 216.7±6.6), and adhesion ability of matrix protein (from 99.0±8.5 to 152.0±12.3) through FAK/Src/Rac1 signaling pathway in GC.(all P<0.05) Conclusions: ITGA5 acts as a cancer-promoting factor in GC. The current study provides theoretical evidence for probing the novel molecular targets for the treatment of GC.

[Diagnosis and treatment of gastric cancer with immediate double primary carcinoma].

Objective: To investigate the clinical characteristics, treatment and prognosis of gastric cancer complicated with immediate double primary cancer. Methods: The clinical data of patients who met the diagnostic criteria of gastric cancer with immediate double primary cancer from January 2016 to June 2019 were analyzed retrospectively. Results: There were 29 cases of gastric cancer with immediate double primary carcinoma, accounting for 1.7% of the 1 741 patients with gastric cancer in the same period. Of these, 17 (58.6%) were more than 70 years of age. 25 cases (86.2%) were male. The postoperative pathological staging was mainly for early gastric cancer (63.2%). Colorectal cancer accounted for 8 cases (27.6%), followed by esophageal cancer in 7 cases (24.1%). The others included 6 cases of lung cancer (20.7%), 2 cases of pancreatic cancer (6.9%), 2 cases of prostate cancer (6.9%), 1 case of non-Hodgkin's lymphoma (3.4%), 1 case of ampullary tumor (3.4%), 1 case of bile duct carcinoma (3.4%) and 1 case of laryngeal carcinoma (3.4%). The prognosis of the surgical treatment group was significantly better than that of the non-surgical treatment group (median survival time: 21.0 months vs 13.0 months, P=0.014). Conclusion: Gastric cancer complicated with immediate double primary cancer mostly occurs in elderly men and early gastric cancer patients. In the complicated tumor, colorectal cancer is the main cause, so we should pay attention to the screening of digestive system. Radical surgery should be performed as far as possible for each primary tumor.

Environmental Exposure-Associated Human Health Risk of Dioxin Compounds in the Vicinity of a Municipal Solid Waste Incinerator in Shanghai, China.

In order to assess environmental exposure-associated human health risk of dioxin compounds for the population in the vicinity of a municipal solid waste incinerator (MSWI) in Shanghai, the atmospheric samples (n = 24) and soils samples (n = 96) were collected and analyzed to obtain the concentration level, pollution characteristics and seasonal changes of dioxin compounds in environmental medias. The toxicity equivalent concentration range of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) was 30.9-409 fg WHO-TEQ·m-3 in atmosphere and 0.362-8.55 ng WHO-TEQ·kg-1 in soil. The non-carcinogenic health risk and carcinogenic health risk from PCDD/Fs environmental exposure of people living in the vicinity of the MSWI in Shanghai were all within the allowable range of the US Environmental Protection Agency, which implied that the MSWI in Shanghai did not produce additional risk for the population living in its vicinity.

[Discussion on early warning, prevention and control of emerging infectious diseases from a macroscopic perspective based on big data and effective distance model: enlightenment of COVID-19 epidemic data in China].

Objective: To provide a system for warning, preventing and controlling emerging infectious diseases from a macroscopic perspective, using the COVID-19 epidemic data and effective distance model. Methods: The dates of hospitalization/isolation treatment of the first confirmed cases of COVID-19 and the cumulative numbers of confirmed cases in different provinces in China reported as of 23 February, 2020 were collected. The Location Based Service (LBS) big data platform of "Baidu Migration" was employed to obtain the data of the proportion of the floating population from Wuhan to all parts of the country. Effective distance models and linear regression models were established to analyze the relationship between the effective distance and the arrival time of the epidemic as well as the number of cumulative confirmed cases at provincial and municipal levels. Results: The arrival time of the epidemic and the cumulative number of confirmed cases of COVID-19 had significant linear relationship at both provincial and municipal levels in China, and the regression coefficients of each linear model were significant (P<0.001). At the provincial level, the effective distance could explain about 71% of the variation of the model with arrival time along with around 90% of the variation for the model in the cumulative confirmed case magnitude; at the municipal level, the effective distance could explain about 66% of the variation for the model in arrival time, and about 85% of the variation of the model with the cumulative confirmed case magnitude. Conclusions: The fitting degree of the models are good. The LBS big data and effective distance model can be used to estimate the track, time and extent of epidemic spread to provide useful reference for early warning, prevention and control of emerging infectious diseases.

Let-7 participates in the regulation of inflammatory response in spinal cord injury through PI3K/Akt signaling pathway.

OBJECTIVE: To study the potential mechanism of let-7 in participating in the regulation of inflammatory response in spinal cord injury (SCI). MATERIALS AND METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into four groups: group A (Sham, n=10), group B (SCI+NC, n=10), group C (SCI+antagomir, n=10), and group D (SCI+mimics, n=10). The SCI model was established via operation in all groups. After successful modeling, let-7-antagomir negative control (80 mg/kg) was intraperitoneally injected in SCI+NC group at 5 d, an equal amount of let-7-antagomir was intraperitoneally injected in SCI+antagomir group at 5 d, and an equal amount of let-7-mimics was intraperitoneally injected in SCI+mimics group at 5 d. The inflammatory cells in experimental groups and control group were observed via hematoxylin-eosin (HE) staining. At the same time, the expression of let-7 in the four groups was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the expressions of phosphatidylinositol 3-hydroxy kinase (PI3K) and protein kinase B (Akt) in all groups were detected via Western blotting, and the inflammatory index levels in each group were detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: In Sham group, it was observed via HE staining that there were only a few bleeding or inflammatory cells. In SCI+NC group, bleeding and inflammatory cells basically tended to be stable. There were a large number of inflammatory cells in SCI+mimics group, while there were some inflammatory cells in SCI+antagomir group, but showing a decreasing trend compared with SCI+NC group. It was found in the RT-PCR detection of let-7 expression level in all groups that the expression of let-7 significantly declined in SCI+antangomir group compared with that in Sham group and SCI+NC group, and there were significant differences (p<0.01). The expression of let-7 was significantly increased in SCI+mimics group compared with that in Sham group and SCI+NC group, and there were significant differences (p<0.01). The results of Western blotting revealed that the PI3K and Akt protein expressions were significantly decreased in SCI+mimics group compared with those in SCI+antagomir group, SCI+NC group, and Sham group (p<0.05). The ELISA results showed that the levels of inflammatory factors in SCI+mimics group, SCI+antagomir group, and SCI+NC group were significantly higher than those in Sham group. In SCI+mimics group, the levels of inflammatory factors were abnormally high and reached extremely significant levels (p<0.05), indicating that let-7 promotes the inflammatory response after SCI. CONCLUSIONS: Let-7 participates in the regulation of inflammatory response in SCI through the PI3K/Akt signaling pathway.

GAS5 promotes podocyte injury in sepsis by inhibiting PTEN expression.

OBJECTIVE: To investigate the potential role of long noncoding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) in sepsis-induced podocyte injury and its underlying mechanism. MATERIALS AND METHODS: The sepsis model was established by lipopolysaccharide (LPS) induction in podocytes. The expression levels of Nephrin and GAS5 were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) after LPS induction in podocytes for 12 h, 24 h and 36 h, respectively. Western blot was used to detect the expression level of Nephrin in sepsis-induced podocytes. The mRNA expressions of GAS5 and Nephrin in podocytes were detected after transfection of GAS5 siRNA. Albumin influx in podocytes after GAS5 knockdown was detected by Transwell assay. Western blot was used to detect the protein expression of Snail in sepsis after GAS5 knockdown. The target gene of GAS5 was predicted by bioinformatics analysis. QRT-PCR and Western blot were used to detect the protein and mRNA levels of PTEN (phosphatase and tensin homolog deleted on chromosome ten). Nephrin expression and the albumin inflow after PTEN knockdown were then measured. The expression of PI3K/AKT/GSK3ß was also detected after GAS5 was downregulated while PTEN was upregulated. RESULTS: LPS stimulation downregulated the mRNA expression of Nephrin in podocytes and achieved the lowest level at 24 h. The protein expression change of Nephrin was consistent with its mRNA expression. In the septic state, the albumin influx of podocytes remarkably increased, but the function of podocyte barrier was weakened. Besides, GAS5 expression decreased in a time-dependent manner in LPS-induced podocytes. After GAS5 knockdown by siRNA, Nephrin expression and the function of podocyte barrier were significantly reduced. Snail expression was also upregulated in septic state, and GAS5 knockdown increased the expressions of phosphorylated Snail and PI3K/AKT/GSK3ß. After knockdown of GAS5, the mRNA and protein levels of PTEN significantly decreased, which was contract to the expression of Snail. However, overexpression of PTEN could reverse the promotive effect of GAS5 on PI3K/AKT activation. CONCLUSIONS: GAS5 expression decreased in sepsis-induced podocyte injury, and GAS5 was involved in regulating sepsis-induced podocyte injury by reducing PTEN expression.

Seawater Incursion Events in a Cretaceous Paleo-lake Revealed by Specific Marine Biological Markers.

Many large paleo-lakes in North China were formed after the Triassic Era. Seawater incursion events (SWIEs) in these lakes have been extensively discussed in the literature, yet lack reliable methodology and solid evidence, which are essential for reconstructing and confirming SWIEs. The present study employs specific marine biological markers (24-n-propyl and 24-isopropyl cholestanes) to trace SWIEs in a dated core taken from the Songliao Basin (SLB). Two SWIEs were identified. The first SWIE from 91.37 to 89.00 Ma, was continuous and variable but not strong, while the second SWIE from 84.72 to 83.72 Ma was episodic and strong. SWIEs caused high total organic carbon (TOC) and negative δ(13)Corg values in the sediments, which were interpreted as an indication of high productivity in the lake, due to the enhancement of nutrient supplies as well as high levels of aqueous CO2, due to the mixing of alkaline seawater and acidic lake water. The SWIEs in SLB were controlled by regional tectonic activity and eustatic variation. Movement direction changes of the Izanagi/Kula Plate in 90 Ma and 84 Ma created faults and triggered SWIEs. A high sea level, from 90 to 84 Ma, also facilitated the occurrence of SWIEs in SLB.

Optical property study of FePt-C nanocomposite thin film for heat-assisted magnetic recording.

Optical properties of the FePt-C nanocomposite thin film that was synthesized by sputtering with MgO/NiTa underlayer on glass substrate have been determined by an approach combining spectroscopic ellipsometry and transmission over the wavelength range of 380 - 1700 nm. It was observed that the refractive index is larger than the extinction coefficient, indicating that free electron absorption is not the dominant optical transition in the FePt-C thin film. Compared with FePt thin film, the FePt-C thin film has smaller optical constants, which lead to better optical performance including smaller optical spot on recording media and higher transducer efficiency for heat assisted magnetic recording.

IMM-H004, a novel coumarin derivative compound, protects against amyloid beta-induced neurotoxicity through a mitochondrial-dependent pathway.

We have investigated the effect of IMM-H004 (7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one), a coumarin derivative, on the amyloid beta (Aß)-induced neurotoxicity in primary culture cortical neurons and pheochromocytoma (PC12) cells. Our results showed that treatment with IMM-H004 markedly reduced the number of apoptotic cells after exposure to Aß25-35 or Aß1-42, determined by MTT, TUNEL staining and Flow cytometry. Further study indicated that IMM-H004 significantly inhibited Aß-induced cytotoxicity and apoptosis by reversing Aß-induced mitochondrial dysfunction, including MMP (mitochondrial membrane potential) decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. IMM-H004 can regulate the interaction between Bax and Bcl-2, decreased levels of p53 and active caspase-3 protein induced by Aß25-35. Furthermore, IMM-H004 also reduced translocation of AIF (apoptosis-inducing factor) induced by Aß25-35. These results demonstrated that IMM-H004 was capable of protecting neuronal cells from Aß-induced degeneration through a mitochondrial-dependent apoptotic pathway. The results of this study lend further credence to the notion that IMM-H004 is a 'multipotent therapeutic agrent' that reduces toxic levels of brain Aß, and holds the potential to protect neuronal mitochondrial function in Alzheimer's disease.

Nanogranular L1(0) FePt-C-Ta2O5 composite media for perpendicular recording applications.

In this report, the effect of simultaneously adding two dopants (C and Ta2O5) in FePt was investigated. (Fe55Pt45)79C21-(x vol%) Ta2O5 films (where x = 0% to 20%) were prepared using both low and high power magnetron sputtering on MgO (2 nm)/CrRu (30 nm) underlayers with in-situ heating at 350 degrees C. Films deposited at low power showed a decrease in exchange coupling with increasing Ta2O5 content. Out-of-plane coercivity of 7.2 kOe was observed even with up to 20 vol% Ta2O5. X-Ray diffraction spectra showed presence of FePt(001) texture for all compositions of Ta2O5 ranging from 0 to 20 vol% suggesting that the perpendicular anisotropy was maintained even with up to 20 vol% of dopant content. Films deposited at high power showed a different behavior with an initial increase in out-of-plane coercivity to 8.2 kOe and a reduction in exchange coupling with loop slope parameter (alpha) approaching a fully decoupled value of 1. Further increase in doping content led to deterioration in the out-of-plane coercivity, as well as an increase in the exchange coupling.

Interlayer exchange coupling effect of L1(0) CoPt based exchange coupled composite media.

In this work, effects of exchange coupling of soft magnetic layer on switching field and magnetization reversal behaviour of CoPt-SiO2(soft)/CoPt-SiO2(hard) exchange coupled media were investigated. With increasing the thickness of the soft layer, both the coercivity and magnetization squareness of composite media decreased. Soft layer thickness 4 nm and below was more effective to significantly reduce the switching field than that above 4 nm. More incoherent switching behavior was observed with increasing soft layer thickness.

NiW/Ru underlayer for CoPt-SiO2 granular perpendicular recording media.

This paper presented the usage of the NiW/Ru underlayer to replace the single Ru underlayer for promoting CoPt hcp (0002) texture. Fcc (111) textured NiW film was used to induce the Ru hcp (0002) texture. It was found that the utilization of the (111) textured NiW alloying layer promoted the formation of Ru(0002) texture, enhanced the magnetic grain isolation and generated the uniform grains with gain size less than 10 nm in CoPt-SiO2 recording layer. The out-of-plane coercivity was also enhanced with the growth of 10 nm NiW underlayer below the Ru layer.

Nanostructured SmCo5 thin films with perpendicular anisotropy formed in a wide range of Sm-Co compositions.

In this work, we prepared SmCo5 thin films with (0001) texture exhibiting perpendicular anisotropy in a wide range of Sm(x)Co(100-x) compositions (x = 13.2 approximately 37.0) on Cu/Ta underlayers. At a composition of Sm16.7Co83.3 (SmCo5), the SmCo5 film exhibits a maximum perpendicular coercivity of 18.2 kOe, which is attributed to a good crystallinity and an excellent (000l) texture. The SmCo5 (000l) peaks are shifted to smaller angles compared to the standard powder sample which indicates the formation of a SmCoCu alloy through Cu diffusion. The EDX result for this sample gives a composition of SmCo3Cu2.1 which confirms Cu diffusion into the SmCo5 layer. TEM image shows that SmCo5 film is well crystallized with a grain size of 50 nm.

FeTaC magnetic soft underlayer for L1(0) FePt based perpendicular recording media.

FeTaC magnetic soft underlayer under elevated temperature process conditions for L1(0) FePt based perpendicular recording media has been investigated. After annealing FeTaC for 40 min at 350 degrees C, saturation moment increases to 750 emu/cm3 and, coercivity and remanent moment reduce to 2.3 Oe and 166 emu/cm3 respectively. The microstructure of FeTaC annealed at 350 degrees C for 40 min composes of Fe nanocrystals with random orientations immersed in an amorphous matrix. FeTaC surface roughness due to elevated temperature process is reduced by 100 W RF plasma etching and CrRu with (200) orientation is developed. It is found that changing elemental composition due to C diffusion into the CrRu layer and RF preferential etching over Fe, Ta and C has the influence on the magnetic properties of FeTaC.

Models describing nonlinear interactions in graded neuron synapses.

An intracellular recording made from the retinal luminosity horizontal cell (LHC) demonstrated that repetitive red flashes enhanced the cell's responsiveness to red stimulus and depressed its responsiveness to green stimulus and that repetitive green flashes suppressed the cell's red response but produced little change in its green response. Based on the idea that the spectral plasticity of LHCs may reflect some synaptic efficacy changes between the LHC and various cones, a self-organizing system is proposed to investigate the possible manner of information processing and storage within the synapses. The results of model analysis suggest that the stimulus-pattern-related spectral plasticity is attributable to the excitatory interaction within the same kinds of synapses and the inhibitory interaction between different kinds of synapses. This system is able to encode and store the history of signal transmission in a graded and cumulative fashion.

Marine natural products as lead anti-HIV agents.

Current anti-HIV drugs have extreme side effects and resistance to these drugs develops rapidly. The marine environment holds an unprecedented number of unusual chemical structural classes with activity against HIV. We review the literature on anti-HIV activity of marine natural products and discuss the efficacy of different structural classes.

Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development.

Direct genetic manipulations have shown that telomerase-mediated telomere elongation plays a key role in determining cellular replicative capacity and senescence. The mechanisms regulating the production of an active telomerase enzyme are still predominantly unknown, although roles for transcriptional control of hTERT, alternative-splicing of hTERT transcripts, and post-translational phosphorylation of hTERT protein have been advocated. Here we show that hTERT is alternatively spliced in specific patterns by different tissue types during human development. Alternative splicing often prohibits the expression of hTERT protein containing functional reverse transcriptase domains. In these instances, telomerase activity is absent, leading to shortening of telomeres. The specific pattern of hTERT mRNA variants in human development provides evidence that alternative splicing is non-random and participates in the regulation of telomerase activity.

Examining histone acetlylation at specific genomic regions.

The acetylation of core histones can modulate the expression of numerous genes. In general, the deacetylation of histones results in transcriptional repression, whereas increases in histone acetylation lead to the enhancement of gene transcription. Since histone acetylation is maintained during mitosis, the acetylation pattern may contribute a heritable epigenetic imprint that can continue to influence gene transcription (1). These findings suggest that the degree of histone acetylation may represent one of several nonexclusive mechanisms that can initiate or maintain the allele-specific silencing of genomic imprinting. We have recently shown that the inhibition of histone deacetylation by Trichostatin A (TSA) induces the expression of the normally imprinted maternal IGF2 allele (2), leading to biallelic expression in both human and murine cells. Partial loss of imprinting of both sense and antisense Igf2r is also observed after TSA treatment. It has also been shown that exposure of mouse conceptuses to TSA leads to loss of H19 imprinting (3). In X-chromosome inactivation, the inactive chromosome is associated with relatively underacetylated histones (4). Changes in histone acetylation become apparent after the expression of Xist, the gene responsible for X-chromosome gene silencing, and after the downregulation of the inactivated X-chromosome genes (5), suggesting that decreased histone acetylation may mark or otherwise stabilize transcriptional repression rather than actually initiate it.

An in vitro study of the structure-activity relationships of sulfated polysaccharide from brown algae to its antioxidant effect.

In this paper, the structure-activity relationships of chemically modified uronic acid polymer fragments from brown algae with regard to their antioxidant effects on H2O2-damaged lymphocyte were studied. The results indicated that the most potent antioxidant activity was obtained from the sulfated polysaccharide with ratio of mannuronate blocks (M-blocks) to guluronate blocks (G-blocks) of 3 to 1 and carboxyl residue unesterified. The sulfated G-blocks with esterified carboxyl residue also prevented lymphocyte from injury. However, the sulfated G-blocks bearing unesterified carboxyl residue hardly exerted antioxidant activity. These findings suggested that both M-blocks and esterified carboxyl residue were determinant structures in preventing lymphocyte from being oxidized by H202, indicating that the existence of M-blocks was more important in scavenging free radicals.

Allele-specific histone acetylation accompanies genomic imprinting of the insulin-like growth factor II receptor gene.

The mouse insulin-like growth factor II receptor (Igf2r) gene encodes two reciprocally imprinted RNA transcripts: paternally imprinted Igf2r sense and maternally imprinted Igf2r antisense. Although DNA methylation has been implicated in the initiation and maintenance of genomic imprinting, acetylation of core histones has recently been appreciated as another important factor that regulates gene expression. To determine whether histone acetylation participates in the regulation of Igf2r imprinting, we examined the relative abundance of acetylated histones in interspecific mice (M. spretus x C57BL/6). Oligonucleosomes derived from liver were immunoprecipitated with acetyl-histone antiserum and were analyzed for the allelic distribution of DNA from the region of the sense and antisense Igf2r promoters. In nucleosomes associated with the Igf2r sense promoter, histone acetylation was demonstrated on the maternal allele, which is transcriptionally active. There was much less histone acetylation on the suppressed paternal allele. In nucleosomes associated with the Igf2r antisense promoter, the active paternal allele was heavily acetylated, whereas the suppressed maternal allele was underacetylated. Treatment of cultured fibroblasts with the histone deacetylase inhibitor Trichostatin A induces partial relaxation of genomic imprinting as well as decreased DNA methylation of both Igf2r sense and antisense promoters. These results demonstrate that increases in histone acetylation can lead to decreased DNA methylation, thereby modulating the regulation of the imprinted expression of Igf2r sense and antisense transcripts.