Squamous cell carcinoma of ascending colon with pMMR/MSS showed a partial response to PD-1 blockade combined with chemotherapy: A case report.

Primary colon squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. Moreover, there is no treatment guideline for this disease. Proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal adenocarcinoma is refractory to immune monotherapy. Although the combination of immunotherapy with chemotherapy in pMMR/MSS colorectal cancer (CRC) is currently under investigation, the clinical activity of this approach in colorectal SCC remains unknown. In this article, we report the case of a pMMR/MSS CRC patient with ascending colon SCC who had high programmed cell death-ligand 1 (PD-L1) expression and the a missense mutation in codon 600 of the B-Raf proto-oncogene (BRAF V600E) mutation. The patient exhibited a significant response to the combination of immunotherapy and chemotherapy. After eight cycles of treatment with the combination of sintilimab and mFOLFOX6 (oxaliplatin, fluorouracil, and leucovorin), computed tomography-guided microwave ablation of the liver metastasis was performed. The patient achieved excellent durable response and continues to experience a good quality of life. The present case indicates that programmed cell death 1 blockade combined with chemotherapy may be an effective therapy for patients with pMMR/MSS colon SCC and high PD-L1 expression. Furthermore, PD-L1 expression may be a biomarker for immunotherapy in patients with colorectal SCC.

Rapid fabrication of sub-micron scale functional optical microstructures on the optical fiber end faces by DMD-based lithography.

The rapid development of optical fiber application systems puts forward higher requirements for the miniaturization and integration of optical fiber devices. One promising solution is to integrate diffractive optical microstructures on the end faces of optical fibers. However, rapid microfabrication on such tiny and irregular substrates is a challenge. In recent years, Femtosecond laser polymerization technology has become an effective solution to the challenge, which can be flexibly applied for the fabrication of complex 3D microstructures with ultra-high resolution. When the demand for the lithography resolution is not very high, other microfabrication methods with a lower technical threshold may be developed for achieving a balance between fabrication precision, cost and efficiency. In this paper, we report a Digital Micromirror Device (DMD) based lithography method dedicated to the fabrication of functional optical microstructures on the optical fiber end faces. Especially, it's also applicable to single-mode fibers (SMFs). By the projection via a 40x objective lens, the fabrication resolution of 0.405 µm was achieved within an exposure area of 209.92 µm × 157.44 µm. We evaluated the microfabrication results by the photomicrographs and the optical diffraction modulation effects of the functional optical microstructures. This method provides a new idea for fabricating both hybrid optical fiber devices and SMF devices, and it may be an alternative method for resolving the conflict between the precision, the cost and the efficiency.

A Layer-Dependent Analytical Model for Printability Assessment of Additive Manufacturing Copper/Steel Multi-Material Components by Directed Energy Deposition.

Copper/steel bimetal, one of the most popular and typical multi-material components (MMC), processes excellent comprehensive properties with the high strength of steel and the high thermal conductivity of copper alloy. Additive manufacturing (AM) technology is characterized by layer-wise fabrication, and thus is especially suitable for fabricating MMC. However, considering both the great difference in thermophysical properties between copper and steel and the layer-based fabrication character of the AM process, the optimal processing parameters will vary throughout the deposition process. In this paper, we propose an analytical calculation model to predict the layer-dependent processing parameters when fabricating the 07Cr15Ni5 steel on the CuCr substrate at the fixed layer thickness (0.3 mm) and hatching space (0.3 mm). Specifically, the changes in effective thermal conductivity and specific heat capacity with the layer number, as well as the absorption rate and catchment efficiency with the processing parameters are considered. The parameter maps predicted by the model have good agreement with the experimental results. The proposed analytical model provides new guidance to determine the processing windows for novel multi-material components, especially for the multi-materials whose physical properties are significantly different.

[Difference of soil nematode communities between the humus and soil surface layer in the cold temperate coniferous and broadleaved mixed forest of Yulong Snow Mountain Nature Reserve, Yunnan, China]. / çŽ‰é¾™é›ªå±±è‡ªç„¶ä¿æŠ¤åŒºå¯’æ¸©æ€§é’ˆé˜”æ··äº¤æž—è æ®–è´¨å±‚å’ŒåœŸå£¤è¡¨å±‚çº¿è™«ç¾¤è½ç»“æž„å·®å¼‚.

A high-throughput sequencing approach was used to differentiate the nematode communities in the humus and soil surface layer (0-10 cm) in 20 hm2 plot located in the cold temperate coniferous and broadleaved mixed forest of Yulong Snow Mountain Nature Reserve, Lijiang, Yunnan. A total of 5744582 sequences were obtained, which were further annotated to 44 nematode families. In the humus layer, 37 families were recorded, with Tylenchidae (18.1%) being the most dominant family. For trophic groups, bacterivorous, fungivorous and herbivorous were predominant. The soil surface layer had 41 families, with Mononchidae (45.4%) being the most dominant family. The relative abundance of predatory nematode was highest in the soil surface layer. There was no significant difference in the α diversity indices (Shannon, Simpson and Chao1 index) of nematode communities at the OTU level between two habitats. At the family level, however, α diversity of nematode community in the humus layer was significantly lower than in soil surface layer. ß diversity of the nematode community was significantly different in the two habitats, with lower Cody index but high Sorensen non-similarity index in the humus habitat. Results of non-metric multidimensional scaling (NMDS) analysis showed that the internal structure difference of nematode community in the soil surface layer was higher than that in the humus layer.

Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer.

Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice. Human NK cells were isolated from peripheral blood mononuclear cells and cultured for expansion in vitro. The present results demonstrated that ovarian cells in BALB/c-nude mice did not induce spontaneous ovarian cancer cell metastasis in the NK-treated group. In addition, NK cells activated immune cells in the immune system, which resulted in inhibition of ovarian tumor growth in vitro and in a murine xenograft model of ovarian cancer. The data also indicated that cytotoxic activity of NK cells prevented migration and invasion of ovarian cancer cells, which contributed to prevention of systemic metastasis and suggested that NK cells could be effective cells for therapy against ovarian cancer. Furthermore, NK cells induced apoptosis and increased the number of cluster of differentiation (CD)4+, CD8+ as well as cytotoxic T lymphocyte responses by intravenous injection in a murine xenograft model of ovarian cancer. These results suggested that NK cells inhibited the systemic metastasis for ovarian cancer cells. In conclusion, the present study suggested that NK cell immunotherapy inhibited systemic metastasis of ovarian cancer cells and improved the survival rate of mice. Sufficient supplementation of NK cells may serve as a promising immunotherapeutic strategy for ovarian cancer.

Stevioside induced cytotoxicity in colon cancer cells via reactive oxygen species and mitogen-activated protein kinase signaling pathways-mediated apoptosis.

The role of mitogen-activated protein kinase (MAPK) signaling pathways in cell growth and differentiation has been well established. The present study aimed to investigate the anti-proliferative effect of stevioside on human colon cancer HT-29 cells. Additionally, the effect of stevioside on cell cycle arrest and MAPK signaling pathways in HT-29 cells was explored. Stevioside was observed to significantly inhibit cancer cell growth at a dose of 5 µM at 48 and 72 h. A dose-dependent increase in the apoptosis rate was observed with cell cycle arrest at G2/M phase. In addition, caspase-9 and caspase-3 activity also increased. An increase in reactive oxygen species (ROS) production and a decrease in the mitochondrial membrane potential indicated that the mitochondrial-mediated intrinsic pathway is responsible for apoptotic activity. These results were additionally verified by the elevated expression level of phosphorylated p38 and extracellular signal-regulated kinase mitogen-activated protein kinases (MAPKs). Additionally, by inhibiting ROS production and MAPK activation, the antiproliferative effect of stevioside was suppressed, confirming the hypothesis that ROS and MAPK proteins induce apoptosis in human colon cancer HT-29 cells.

Long non-coding RNA TUG1 promotes cell proliferation and metastasis in human breast cancer.

BACKGROUND: Long non-coding RNAs (LncRNAs) utilize a wide variety of mechanisms to regulate RNAs or proteins on the transcriptional or post-transcriptional levels. Accumulating studies have identified numerous LncRNAs to exert critical effects on different physiological processes, genetic disorders, and human diseases. MATERIALS AND METHODS: Both clinical tissues from breast cancer patients and cultured cells were used for the qRT-PCR analysis. Specific siRNAs were included to assess the roles of TUG1 with cell viability assay, transwell assay, and cell apoptosis assay, respectively. RESULTS: The expression of TUG1 was enhanced in breast cancerous tissues and in highly invasive breast cancer cell lines and was associated with clinical variables, including tumor size, distant metastasis and TNM staging. Knockdown of TUG1 significantly slowed down cell proliferation, cell migration, and invasion in breast cancer cell lines MDA-MB-231 and MDA-MB-436. In addition, cell apoptotic rate was shown to increase upon siTUG1 treatment as evidenced by increases of the activities of caspase-3 and caspase-9. CONCLUSION: The identification of TUG1 as a critical mediator of breast cancer progression implied that it might serve as a biomarker for the diagnosis and treatment of breast cancer in clinic.

Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice.

Heme oxygenase (HO) is the rate-limiting enzyme in heme metabolism. HO-1 exhibits anti-oxidative and anti-inflammatory function via the actions of its metabolite, respectively. A growing body of evidence demonstrates that HO-1 is implicated in the pathogenesis and progression of several types of cancer. However, whether HO-1 takes part in healthy-premalignant-malignant transformation is still undefined. In this study, we took advantage of transgenic mice which over-expressed HO-1 dominant negative mutant (HO-1 G143H) and observed its susceptibility to DEN-induced hepatocarcinogenesis. Our results indicate that HO-1 G143H mutant accelerates the progression of tumorigenesis and tumor growth. The mechanism is closely related to enhancement of ROS production which induce more hepatocytes death and secretion of inflammatory cytokines, proliferation of surviving hepatocytes. Our result provides the direct evidence that HO-1 plays an important protective role in liver carcinogenesis. Alternatively, we suggest the possible explanation on effect of HO-1 promoter polymorphism which involved in tumorigenesis.

[Vertical Distribution Characteristics and Analysis in Sediments of Xidahai Lake].

The organic matter (OM), total nitrogen (TN), total phosphorus (TP), the morphological changes of phosphorus and the particle size in columnar sediment core of Xidahai Lake were analyzed, to discuss the vertical distribution characteristics and influencing factors. The results showed that the contents of OM, TN and TP were 0. 633% -2. 756%, 0. 150% -0. 429% and 648. 00 - 1 480.67 mg . kg-1 respectively. The contents of Ca-P, IP and OM changed less, the contents of Fe/Al-P, OP, TP and TN fluctuated from 1843 to 1970; The contents of Ca-P, IP and TP tended to decrease, the contents of Fe/Al-P, OP and OM first decreased and then increased to different degree, TN fluctuated largely from 1970 to 1996; The nutrient elements contents showed relatively large fluctuation from 1996 to 2009, the average contents of Fe/Al-P, OP and OM were the highest in the three stages. The sediment core nutrients pollution sources were mainly from industrial wastewater, sewage and the loss of fertilizers of Xidahai Lake. The ratio of C/N in the sediments showed that organic matter was mainly from aquatic organisms. The sediment particle size composition was dominated by clay and fine silt. The correlation studies showed that Ca-P, IP and TP were significantly positively correlated, showing that the contribution of Ca-P to IP and TP growth was large.

The effect of simple nitrogen fertilizer recommendation strategies on product carbon footprint and gross margin of wheat and maize production in the North China Plain.

Overuse of nitrogen (N) fertilizer constitutes the major issue of current crop production in China, exerting a substantial effect on global warming through massive emission of greenhouse gas (GHG). Despite the ongoing effort, which includes the promotion of technologically sophisticated N management schemes, farmers' N rates maintain at excessive rates. Therefore the current study tests three simple and easily to apply N fertilizer recommendation strategies, which could be implemented on large scale through the existing agricultural advisory system of China, at comparatively low cost. Building on a detailed crop production dataset of 65 winter wheat (WW) and summer maize (SM) producing farm households of the North China Plain, scenario analysis is applied. The effects of the three N strategies under constant and changing yield levels on product carbon footprint (PCF) and gross margin (GM) are determined for the production condition of every individual farm household. The N fixed rate strategy realized the highest improvement potential in PCF and GM in WW; while the N coefficient strategy performed best in SM. The analysis furthermore revealed that improved N management has a significant positive effect on PCF, but only a marginal and insignificant effect on GM. On the other side, a potential 10% yield loss would have only a marginal effect on PCF, but a detrimental effect on farmers' income. With farmers currently applying excessive N rates as "cheap insurance" against potential N limitation, it will be of vital importance to avoid any yield reductions (caused by N limitation) and respective severe financial losses, when promoting and implementing advanced fertilization strategies. To achieve this, it is furthermore recommended to increase the price of fertilizer, improve the agricultural extensions system, and recognize farmers' fertilizer related decision-making processes as key research areas.

Assessment of potential risks associated with heavy metal contamination in sediment in Aobaopao Lake, China, determined from sediment cores.

Lianhuan Lake is found in the lowest point of the Songnen Plain in Eastern China and is a typical hardwater lake. Lianhuan Lake is constituted by eighteen lakes and Aobaopao Lake is located in the eastern portion. Geochemical features and pollution history of heavy metals in Aobaopao Lake were investigated. Total metal contents and chemical fractionations of Cu, Fe, Mn, Ni, Pb, Cd, Cr and Zn were analyzed for core sediment samples taken from north sampling site for Core AB1 and south sampling site for Core AB2 of the lake using the speciation extraction procedure proposed by the Commission of the European Communities Bureau of Reference (BCR) together with grain size and TOC measurements. Heavy metal analyses showed that sediments have similar geochemical features. In order to quantify the anthropogenic contamination of the metals according to their speciation composition, the RSP approach was applied. In Core AB1, Cd is moderate and significant contaminate while Mn is minor, moderate and significant contamination. In Core AB2, Cd is more significant contaminate from 3.75 cm to the surface. The risk assessment code (RAC) established by Perin et al. (Heavy Metals in the Environment, CEP Consultants, Edinburgh, 1985) was used to evaluate the risk of heavy metals in sediments of Aobaopao Lake. The results for both cores suggest that Mn and Cd posed a high risk to local environment.

The vertical variation of nutrients in a sediment core of Delong Lake reveals the anthropogenic effect.

Phosphorus content and its species were studied for the core sediments of Delong Lake, using the SMT sequential extraction method, and then were correlated to the contents of total nitrogen and organic matter. According to (210)Pb and (137)Cs dating, the historical profiles of 33 cm core sediments were generated. The objective of this study was to understand how nutrients of lake sediments evolved in order to get insights into the effect of human activities on their sedimentary history. The nutrients contents in the core sediments slowly increased after 1957, showing the human activity influence the natural deposition of the lake sediment. From 1978 to 1985, various nutrients in the lake sediment rapid increased, showing that the human activities strengthened. From 2003 to now, most of nutrients in the sediment rapidly increased and significantly modified the natural deposition of the lake sediment.

Speciation and distribution characteristics of heavy metals and pollution assessments in the sediments of Nashina Lake, Heilongjiang, China.

Sediment core samples from Nashina Lake, Heilongjiang, China were collected using a gravity sampler. The cores were sliced horizontally at 1 cm each to determine the particle size, total concentrations and speciation of Cd, Cr, Cu, Mn, Ni, Pb, and Zn. Total concentrations of heavy metals were extracted using an acid mixture (containing hydro fluoric acid, nitric acid, and sulphuric acid) and analyzed using an inductively coupled plasma spectrometry. A sequential extraction procedure was employed to separate chemical species. Analysis of results indicate that the concentrations of heavy metals in the sediments of Nashina Lake in descending order are Mn, Cr, Zn, Pb, Ni, Cu, and Cd. The ratios of the average concentrations of four heavy metals (e.g.Cr, Cu, Ni, Zn) to their background values were >1; and those of Mn, Cd, and Pb were >1. Moreover, some toxic metals were mainly distributed in bioavailable fractions. For instance, both Cd and Mn were typically found in Acid-extractable species or Fe-Mn oxide species, and thus can be easily remobilized and enter the food chain. Finally, the analysis of geo-accumulation index showed that anthropogenic pollution levels of Cr, Cu, Mn, Ni, Zn were low, but those of Pb and Cd were at the moderate level. As both Pb and Cd are toxic metals, it is highly necessary to prohibit their transformation and accumulation in the sediments.

[Evolvement and pollution of heavy metals in core sediments from Yamenqi Lake in Lianhuan Lake, China].

One sediment core was obtained from the center of Yamenqi Lake at the Songnen Plain in eastern China in August 2010 using a gravity corer. The sediment samples were digested using HNO3-HClO4-HF. Concentrations of the metals Cr, Cu, Mn, Ni, Fe, Pb, Zn, Cd, Al, Ba, Ca, K, Li, Mg, Na and Sr were determined using inductively coupled plasma-mass spectrometry (ICP-MS). With the dating approach, the characteristics and polluted history of heavy metals in lake sediments were determined. The heavy metal pollution of sediment was discussed based on the enrichment factor. The results are listed as following:(1) the contents of all elements had a smooth variation trend before 1950,and fluctuated severely from 1950 to 1990. The contents of Mn, Zn, Cd, Pb, Fe, Ni, Cr, Cu, Ca, Li and Sr increased obviously since 1990. (2) Mn, Zn, Pb and Cd showed light contamination degree. Contents of Ni, Cr and Cu were below the contamination level.

MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7.

Because it is a member of the miR-106b~25 cluster, microRNA-25 (miR-25) is known to be dysregulated in human cancers. However, the expression and role of miR-25 in colon cancer remain unclear. In this study, miR-25 was found to be down-regulated in human colon cancer tissues when compared to those in matched, non-neoplastic mucosa tissues. Functional studies revealed that restoration of miR-25 expression inhibited cell proliferation and migration. In contrast, miR-25 inhibition could promote the proliferation and migratory ability of cells. Stable over-expression of miR-25 also suppressed the growth of colon cancer-cell xenografts in vivo. Furthermore, bioinformatic predictions and experimental validation were used to identify Smad7 as a direct target of miR-25. Functional reverse experiments indicated that the antitumor effects of miR-25 were probably mediated by its repression of Smad7. These results suggest that miR-25 may function as a tumor suppressor by targeting Smad7 in colon cancer. Thus, miR-25 may serve as a potential therapeutic agent or target for cancer therapy.

[Ichthyofauna and its community diversity in volcanic barrier lakes of Northeast China].

Based on the investigations of fish resources in Jingpo Lake and Wudalianchi Lakes in 2008-2011 and the historical data, this paper analyzed the characteristics of ichthyofauna and its community diversity in volcanic barrier lakes of Northeast China. The ichthyofauna in the volcanic barrier lakes of Northeast China was consisted of 64 native species, belonging to 47 genera, 16 families, and 9 orders, among which, one species was the second class National protected wild animal, four species were Chinese endemic species, and five species were Chinese vulnerable species. In the 64 recorded species, there were 44 species of Cypriniformes order and 37 species of Cyprinidae family dominated, respectively. The ichthyofauna in the volcanic barrier lakes of Northeast China was formed by 7 fauna complexes, among which, the eastern plain fauna complex was dominant, the common species from the South and the North occupied 53.1%, and the northern endemic species took up 46.9%. The Shannon, Fisher-alpha, Pielou, Margalef, and Simpson indices of the ichthyofauna were 2.078, 4.536, 0.575, 3.723, and 0.269, respectively, and the abundance distribution pattern of native species accorded with lognormal model. The Bray-Curtis, Morisita-Horn, Ochiai, Sørensen, and Whittaker indices between the communities of ichthyofauna in the volcanic barrier lakes of Northeast China and the Jingpo Lake were 0.820, 0.992, 0.870, 0.862 and 0.138, respectively, and those between the communities of ichthyofauna in the volcanic barrier lakes and the Wudalianchi Lakes were 0.210, 0.516, 0.838, 0.825, and 0.175, respectively. The ichthyofauna in volcanic barrier lakes of Northeast China was characterized by the mutual infiltration between the South and the North, and the overlap and transition between the Palaeoarctic realm and the Oricetal realm. It was suggested that the ichthyofauna community species diversity in the volcanic barrier lakes of Northeast China was higher, the species structure was more stable, but the species richness trended to decrease.

Historical record and source apportionment of polycyclic aromatic hydrocarbons in the Lianhuan Lake sediments.

Polycyclic aromatic hydrocarbons (PAHs) in a sediment core from the north Lianhuan Lake were collected to investigate its historical changes in the last one hundred years and its possible influence on ecological system in the lake. GC-MS was used to determine the concentrations of PAHs, and sediment chronological age was examined by (137)Cs dating approach. The concentrations of 16 different kinds of PAHs in the sediment samples ranged from 297 to 1,327 ng g(-1), and the low molecular weight (LMW) were predominant. The intensification of industrial and anthropogenic activities in the Daqing oil field may play the key role in the increase of PAHs concentrations in the late 1950s. To the early 1980s, the PAHs concentrations significantly decreased due to the grain size coarsening in the sediment samples, which was confirmed by the precipitation information. The 5-6 rings PAHs concentrations increased in the early 1980s may be attributed to the consumption of petroleum, coal and wood. The results showed that both the PAHs historical record and current concentrations may cause some influence on the Lianhuan Lake ecological system. The toxicology research on this ecological system should be done in the further investigations for determining the PAHs damage on human and ecological system health.