Search

Conformal antennas are practicable candidates to the aerodynamic platforms. A wide-angle scanning conformal phased array antenna for an unmanned aerial vehicle (UAV) platform is designed and presented in this article. An eight-element linear phased array loaded with frequency selective surface (FSS) operating in $S$ -band is investigated. The horizontally polarized antenna element is designed based on a tapered slot feeding dipole. The antenna aperture can be easily conformed to the front wing airframe of the UAV due to the flexibility of the employed polyimide film. To fulfill the requirement of the airborne communication system, two kinds of FSSs are loaded on the dipole antenna to enhance the gain and reduce the 3 dB beamwidth of the main lobe in the elevation plane. To improve the active impedance matching when the beam scans to the large angles, a novel parasitic structure is proposed. Finally, a $1 \times 8$ linear conformal array prototype is simulated, fabricated, and measured. The experimental results indicate that the antenna array achieves a fractional bandwidth of 22.1% with ±70° scanning along the E-plane. The measured results validate the performance of the proposed conformal array and the design.

Polyimide film is a practicable alternative to the conventional substrates utilized in conformal antennas. Due to its flexibility, the antennas based on the polyimide film can be easily conformed to the platform surface. An eight-element linear-phased array operating at the P-band with a wide scan angle is investigated in this letter, which is constructed by the dipoles printed on the polyimide film. The antenna surface is mounted on the front wing of an unmanned aerial vehicle (UAV). Strong coupling is observed between the array elements when the beam scans. Therefore, decoupling structures are loaded in the array elements to broaden the scan angle. To satisfy the requirement of the radar system, directors and reflectors are also employed on the surface of the front wing to narrow the main lobe beamwidth in the elevation plane. The proposed phased array achieves a fractional bandwidth of 16.7% when scanning up to ±60° in the E-plane. The validity of this design is verified by the simulation and measurements of a 1 × 8 array prototype.

Enterocytozoon bieneusi is a common microsporidian species, which can infect humans and various species of animals. However, little is known about E. bieneusi prevalence and genotypes in farmed raccoon dogs (Nyctereutes procyonoides) in Shandong Province, China. In this study, a total of 356 fecal samples were collected from farmed raccoon dogs in Weihai, Weifang, and Yantai cities in Shandong Province, China. A total of 23 (6.5%) samples were E. bieneusi-positive by nested PCR amplification of the internal transcribed spacer (ITS) region of ribosomal DNA. Statistical analysis showed that E. bieneusi prevalence in male raccoon dogs was higher than that in female raccoon dogs, and the highest E. bieneusi prevalence was detected in adult raccoon dogs. Sequence analysis revealed four known E. bieneusi genotypes (D, type IV, CHG1, and Peru8), and type IV (11/23) was the predominant genotype. The genotypes type IV, Peru8, and CHG1 were reported in raccoon dogs for the first time in China. Phylogenetic analysis showed that three human-pathogenic genotypes (D, type IV, and Peru8) were clustered into group 1, and the CHG1 belonged to group 2. These findings expand the current understanding of E. bieneusi prevalence and genotype distribution in raccoon dogs in China. Our study also shows that raccoon dogs are hosts for E. bieneusi belonging to several genotypes, including zoonotic ones, highlighting the possibility of transmission of this pathogen between raccoon dogs and humans.

Indium tin oxide (ITO) material is a practicable alternative to metal utilized in transparent antennas. However, the conductor loss of ITO material is the major obstacle to antenna design. In this communication, an optically transparent reflectarray based on glass substrate with ITO film operating at 28 GHz is presented. A novel sub-wavelength element operating in hybrid modes with $0.167\lambda _{0}$ ( $\lambda _{0}$ is the free-space wavelength at 28 GHz) spacing is proposed for transparent reflectarray design. The peak loss of the proposed element is below 3.4 dB and a phase variation of 420° is achieved at 28 GHz. A $54\times54$ -element reflectarray with a focus to diameter ratio (F/D) of 0.7 is designed and simulated for demonstration. It achieves radiation efficiency higher than 73% at the center operating frequency. The proposed reflectarray is verified by the measurements, which is reasonably consistent with the full-wave simulated results.

Iron removal by goethite is a key procedure in zinc hydrometallurgy. Due to its complex chemical reaction mechanism, multiple reactors cascade, and high uncertainty, it is difficult to optimize and control in industrial process. In this paper, a distributed optimization control method which is based on a novel hybrid model of the iron removal process is proposed. By combining the mechanism model and a data-driven oxygen mass transfer coefficient model, a hybrid model is first established. Then, to overcome the influence of the former reactor on the latter reactor, the ratio of the status in each subsystem to the set point is taken as a new status, and a distributed optimization control problem is constructed. Considering the high dimensionality of this problem, it is necessary to reconstruct it by Virtual Motion Camouflage (VMC), so that the optimal control problem is transformed into a nonlinear constrained optimal trajectory planning problem. And a Legendre pseudo-spectral method is used to solve the problem accurately to obtain the optimal trajectory of the ion concentration. Finally, simulation results show that the proposed method can effectively reflect the industrial process, and track the fluctuation of inlet ion concentrations with a nice real-time performance.

Empathy involves integrated affective and cognitive processes to share the emotional state of others. This evolutionarily conserved ability has also been identified in nonhuman primates and rodents. Our previous work demonstrated that social interaction with a cagemate rat in pain induces mechanical pain hypersensitivity in cagemate observer (CO) rats. Moreover, we also demonstrated that the medial prefrontal cortex (mPFC) and the locus coeruleus-norepinephrine (LC-NE) system are involved in this process. The LC sends noradrenergic innervations throughout the brain, and its innervation of the prefrontal cortex plays important roles in working memory and attention. The present study seeks to study the roles of the LC-to-mPFC pathway in pain empathy in rats. Selective ablation of the noradrenergic innervations of the mPFC through bilateral injections of the axonally transported catecholamine immunotoxin, saporin-conjugated antiserum to dopamine-β-hydroxylase into the mPFC diminished mechanical pain hypersensitivity in CO rats. Bilateral intra-mPFC applications of the adrenergic α1 receptor antagonist prazosin and the β receptor antagonist propranolol, but not the adrenergic α2 antagonist yohimbine, eliminated mechanical pain hypersensitivity in CO rats. In contrast, intra-mPFC applications of prazosin, yohimbine or propranolol did not affect the mechanical pain sensitivity of rats per se. Our results indicate that noradrenergic innervations in the mPFC mediate empathy for pain in rats via the α1 and β receptors.

The construction industry of China is characterized by its huge consumption and carbon emissions, thereby making this industry one of the most important areas that require energy conservation efforts. Identifying those factors that affect carbon emissions in the construction industry carries great significance in reducing building carbon emissions, promoting low-carbon cities, and achieving China’s emission reduction goals. This paper firstly reviews the literature on those factors that affect the carbon emissions in the construction industries of developed countries. Second, by using Henan Province as an example, those factors that influence carbon emissions are measured by using the classical STIRPAT (Stochastic Impacts by Regression on Population, Affluence and Technology) model. Third, some measures for reducing carbon emissions in the construction industry are developed. Those factors that influence the carbon emissions of buildings are multi-dimensional and diversified. Resident population, urbanization rate, building carbon emission intensity, per capita GDP (Gross Domestic Product), and per capita added value of the tertiary industry all have significant effects on the carbon emissions of buildings in Henan Province. Some policy suggestions can be derived from the findings of this work, such as encouraging building energy conservation, improving the energy efficiency of the construction industry, adjusting the use of building materials, and improving the extant policies for building emission reduction. The results also provide a theoretical basis for identifying those factors that affect the carbon emissions in the construction industry and for formulating and implementing strategies for the low-carbon development of this industry.

Enterocytozoon bieneusi is a zoonotic parasite which is considered to be an opportunistic pathogen of humans and animals. A number of studies have reported E. bieneusi infection in various animals. However, no information is available on the occurrence of E. bieneusi in Tan sheep, a unique indigenous sheep species in the Ningxia Hui Autonomous Region, China. The objectives of the present study were to examine the prevalence and identify the genotypes of E. bieneusi in Tan sheep in China. A total of 1014 fecal specimens of Tan sheep from six farms in the Ningxia Hui Autonomous Region were examined by nested PCR amplification of the internal transcribed spacer (ITS) of nuclear ribosomal DNA. The total prevalence of E. bieneusi was 12.2% (124/1014), ranging from 0.5 to 22.2% on six farms. Sequence analysis identified 10 genotypes of E. bieneusi, including three known genotypes, BEB6, COS-I, and CHG13, and seven novel genotypes designated as NX1 to NX7, which all belonged to group 2 by phylogenetic analysis. This is the first report describing the prevalence of E. bieneusi in Tan sheep, and the new genotypes identified in the current study expand the genotype distribution of E. bieneusi. These findings provide baseline data and have implications for the epidemiology and control of E. bieneusi infection in Tan sheep.

Giardia duodenalis is a zoonotic enteric parasite that can infect humans and a number of animal species including rabbits with a worldwide distribution. Infection with G. duodenalis can cause serious public health problems and significant economic losses to animal husbandry. So accurate understanding of the prevalence and genotype distribution of G. duodenalis in rabbits is necessary. In the present study, a total of 616 fecal samples were collected from rabbits in Shandong province, eastern China, and examined in G. duodenalis prevalence and genotypes by nested PCR amplification of β-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi) gene loci of G. duodenalis. Sixty-nine (11.2%) of the examined rabbit fecal samples were G. duodenalis-positive. Of them, the prevalence of G. duodenalis is 8.4% (41/490) in Rizhao city and 22.2% (28/126) in Weihai city. Breeds, region, and feeding modes were highly correlated with G. duodenalis infection in rabbits. Moreover, three genotypes (assemblages A, B, and E) were identified in rabbits at three gene loci, and the assemblage E was the dominant genotype, while the assemblage A was reported in rabbits in China for the first time. It is noticeable that two rabbits were found to be infected with two different G. duodenalis assemblages (assemblages A and E, assemblages B and E, respectively). These findings enrich the genotype distribution of G. duodenalis in rabbits and provide baseline data for preventing and controlling G. duodenalis infection in rabbits in eastern China.

Enterocytozoon bieneusi is a common microsporidian species, which can infect humans and various species of animals. However, little is known about E. bieneusi prevalence and genotypes in farmed raccoon dogs (Nyctereutes procyonoides) in Shandong Province, China. In this study, a total of 356 fecal samples were collected from farmed raccoon dogs in Weihai, Weifang, and Yantai cities in Shandong Province, China. A total of 23 (6.5%) samples were E. bieneusi-positive by nested PCR amplification of the internal transcribed spacer (ITS) region of ribosomal DNA. Statistical analysis showed that E. bieneusi prevalence in male raccoon dogs was higher than that in female raccoon dogs, and the highest E. bieneusi prevalence was detected in adult raccoon dogs. Sequence analysis revealed four known E. bieneusi genotypes (D, type IV, CHG1, and Peru8), and type IV (11/23) was the predominant genotype. The genotypes type IV, Peru8, and CHG1 were reported in raccoon dogs for the first time in China. Phylogenetic analysis showed that three human-pathogenic genotypes (D, type IV, and Peru8) were clustered into group 1, and the CHG1 belonged to group 2. These findings expand the current understanding of E. bieneusi prevalence and genotype distribution in raccoon dogs in China. Our study also shows that raccoon dogs are hosts for E. bieneusi belonging to several genotypes, including zoonotic ones, highlighting the possibility of transmission of this pathogen between raccoon dogs and humans.

Background Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of substantial benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes. Methods We investigated whether ITGAE could be used to discriminate reactive CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1 = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further phenotyping of ITGAE+ cells and the mechanistic basis were investigated. Findings In the training and testing sets from TCGA, ITGAE expression, which is strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently predicted longer disease-free survival (DFS) and overall survival (OS). In line with this, the association between ITGAE+ lymphocytes and survival has been confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the series always co-stained with CD8 were preferentially located in the tumor. Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial–mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. Finally, gene set enrichment analysis showed that immune activation was significantly enriched in the high ITGAE+ TIL group, accompanied by enriched EMT-related pathways. Interpretation Because of the specified expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for the rapid identification of immune infiltration in CRC.

// Xiang Hu 1, 2 , Ya-Qi Li 1, 2 , Qing-Guo Li 1, 2 , Yan-Lei Ma 1, 2 , Jun-Jie Peng 1, 2 and San-Jun Cai 1, 2 1 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 20032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China Correspondence to: San-Jun Cai, email: caisanjun_sh@163.com Keywords: rectal cancer, stage IIA, radiotherapy, outcomes Received: April 25, 2017 Accepted: July 19, 2017 Published: July 29, 2017 ABSTRACT This study sought to determine whether additional radiotherapy is necessary in patients after optimal surgery for stage IIA rectal cancer and how the different covariates influence the efficacy of radiotherapy. The first primary rectal cancer was identified from the 1988–December 2013 Surveillance, Epidemiology and End Results database. We identified 13647 patients with IIA rectal cancer, in which 39.6% received neo-adjuvant radiotherapy and in another 14.96% patients the adjuvant radiotherapy were performed. Neo-adjuvant or adjuvant radiotherapy group had better survival with 10-Year cancer-specific survival estimates as 75.1% and 73.8% compared to 68.4% of no radiotherapy group ( P < 0.01). Adjusted hazard ratio (HR) demonstrated neo-adjuvant and adjuvant radiotherapy (HR: 0.814 and 0.848) were all associated with significantly decreased risk for cancer death. However, radiotherapy did not seem to yield the same survival benefit in selected population. Adjusted stratified analysis demonstrated patients with increasing age, relative large tumor size, and more retrieved regional lymph nodes had no additional benefit for cancer specific survival based on radiation use. In conclusions, unselected patients with stage IIA rectal cancer receiving radiotherapy experienced better survival in comparison to patients without radiation. However, additional radiotherapy is not beneficial for all.

Indium tin oxide (ITO) material is a practicable alternative to metal utilized in transparent antennas. However, the conductor loss of ITO material is the major obstacle to antenna design. In this work, a transparent ITO reflectarray based on glass substrate with ITO film operating at 28GHz is proposed. A single layer sub-wavelength element with 0.31 wavelength spacing is proposed in this reflectarray design. The peak loss of the proposed element is lower than 4dB while achieving a phase variation of 288° at 28GHz. A 30×30 elements reflectarray with a focus to diameter ratio (f/D) of 1 is designed and simulated for demonstration. It achieves more than 84% optical transparency and 75% radiation efficiency at the center frequency.

Front cover: The cover image, by Ming‐Feng Zhou et al., is based on the ORIGINAL ARTICLE Endoplasmic reticulum stress induces apoptosis of arginine vasopressin neurons in central diabetes insipidus via PI3K/Akt pathway. DOI: https://doi.org/10.1111/cns.13089. [Image: see text]

Background It is recommended postoperative adjuvant chemotherapy for all rectal cancers undergoing neo-chemoradiotherapy regardless of the final yield pathology. However, the role of adjuvant chemotherapy in pathological complete response (pCR) remains controversial. We aimed to identify the necessarily of adjuvant chemotherapy in pCR. Methods Consecutive patients with pCR in Fudan University Shanghai Cancer Center (FUSCC) were enrolled. Meanwhile, a pooled analysis of individual patient with pCR was performed from PubMed and Embase databases for validation. Results A total of 171 patients form FUSCC were identified to achieve pCR with up to almost 10 years follow-up. Among them, those receiving adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (log-rank test = 0.17, P = 0.676). The 5y-DFS rates for patients in chemo group and no-chemo group was 87.5 and 88.8%, respectively, showing no significant difference (p = 0.854). No matter chemotherapy regimens, T stage, EMVI and CRM status varied, the results remained consistent. Meantime, the COX model did not demonstrate adjuvant chemotherapy as the independent risk factor for OS and DFS. Additionally, among 18 systemic recurrences in all, the rate of relapse surged rapidly on the 12 months and rose up to peak in the 36th months. In order to validate these results, nine controlled trials involving 5491 patients with pCR were included in this pooled-analysis. For both 5-year overall survival and disease-free survival, the pooling data did not produce a statistically significant effect in cases of adjuvant chemotherapy performed (RR = 0.79 and RR = 0.95, respectively, all p > 0.05). Conclusion This study suggested that rectal cancer patients with pCR did not benefit from adjuvant chemotherapy and we recommended that achievement of pCR require more prolonged close follow care in case of distant metastasis.

A virtual machine (VM) allocation and placement strategy based on the types of applications is proposed.VM is allocated and placed based not only one kind of resource or the available resource of the server, but kinds of resources as well as the available resources of the server.The VM placement consider the available resources of the servers. Unreasonable resource allocation may shorten the service life of physical servers and affect the stability of the cloud data center. To solve this issue, a virtual machine (VM) allocation and placement strategy based on the types of applications is proposed. According to the strategy, appropriate VM is allocated based on the type of application. And the VM is placed on the server that the available resources is sufficient enough to support the application. Meanwhile, the load balance of the server is also considered when the VM is placed. Simulations on Cloudsim platform show that the performance of load balance of the VM placement strategy proposed is much better than that of the traditional VM placement strategy. And extensive experiments on cloudstack show that the VM placement strategy proposed is much more efficient than the traditional VM placement strategy in execution.

Giardia duodenalis is a common intestinal protozoa, which can cause the occurrence of diarrhea, weight loss, and even death in animals or human, this threatens the husbandry industry and public health. It can infect virtually humans and all domestic animals including sheep. Tan sheep is one of the most important sheep breeds, which is short-tailed indigenous sheep breed used for production of high quality meat and pelts in China. However, there are no report regarding the occurrence and multilocus genotyping of G. duodenalis in Tan sheep in northwestern China. Thus, the objective of the present study was to investigate the prevalence and multilocus genotypes of G. duodenalis in Tan sheep. 1014 fecal samples were collected from Tan sheep from Ningxia Hui Autonomous Region, and three loci (β-giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi) genes) were amplified by nested PCR. The prevalence of G. duodenalis in Tan sheep was 14.5% (147/1014), two assemblages (assemblage A, n = 43; and E, n = 90) were detected, including one novel assemblage A at bg locus, one novel assemblage A at tpi locus, and 10 and 11 novel subtypes of assemblage E were detected at the bg and gdh loci, respectively. One MLGs was formed based on sequence variation among the three loci. Moreover, 9 Tan sheep were infected with two assemblages (A and E) based on the three loci. These findings expand the host range of G. duodenalis and revealed genetic diversity of G. duodenalis assemblages in Tan sheep.

Background Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression. Methods The tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis. The effect of OGN on cell proliferation and tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay, immunofluorescence analysis and internalization assay were used for mechanistic study. Results Patients with high expression of OGN were associated with a profound longer survival in CRC and the high serum OGN level was also indicative of fewer recurrences consistently. In colon cancer cells, OGN increased dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment of downstream components of the EGFR internalization machinery (Eps15 and epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to inhibition of epithelial-mesenchymal transition. As results, in vitro and in vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit invasion of colon cancer cells then impede cancer progression. Conclusions There is a positive association between OGN level and prolonged survival in CRC. OGN plays a restrictive role in colorectal cancer progression by reduced activation of EGFR/AKT/Zeb-1.

The Arabidopsis thylakoid membrane bimodular oxidoreductase, AtVKOR, could catalyze disulfide bond formation, and its direct functional domain (thioredoxin-like domain) is located in the thylakoid lumen according to the topological structure. Many proteins have one or several disulfide bonds in the thylakoid lumen, including photosynthetic chain components. A yeast two-hybrid assay was used to identify potential targets for the AtVKOR, and a Trx-like domain was constructed into a BD vector as bait. Twenty-two thylakoid lumenal proteins with disulfides were selected. The cDNAs encoding these proteins were constructed into an AD vector. Eight proteins were identified from the hybrid results to interact with AtVKOR, including HCF164, cytochrome c 6A , violaxanthin deepoxidase, embryo sac development arrest 3 protein (EDA3), two members pentapeptide repeat proteins (TL17 and TL20.3), and two FK-506 binding proteins (FKBP13 and FKBP20-2). The BIACORE system was used to demonstrate that the recombinant HCF164 and Trx-like domain of AtVKOR could interact directly in vitro. The K D value for binding HCF164 to AtVKOR was calculated as 2.5×10 -6 M. These results suggest that AtVKOR can interact with partial thylakoid lumenal proteins and indicates AtVKOR plays an important role in regulating the thylakoid lumen redox.

Two kinds of dynamic load-carrying capacity (DLCC) evaluation methods for free-floating space manipulators (FFSM) in two typical on-orbit operating missions are proposed in this paper. DLCC evaluation is transformed into nonlinear programming problem (NPP) by introducing load-carrying coefficient to measure DLCC: in point-to-point task, penalty function method is adopted to approach the boundary of feasible region rapidly, then DLCC can be obtained through following iterations; in trajectory tracking task, NPP is solved by using multiple one-dimensional search, the dynamic load-carrying coefficient in discontinuous feasible region can be quickly solved through adjusting the searching boundary constantly. The effectiveness of the mentioned methods is verified by simulations.

Background Adjuvant chemotherapy is currently offered routinely, as standard, after radical resection for patients with rectal cancer receiving neo-adjuvant chemoradiation. However, the efficacy of adjuvant chemotherapy in patients with ypTis-2N0M0 has not been documented to the same extent, and the survival benefit remained controversial. The purpose of this work was to determine the role of chemotherapy in patients with ypTis-2N0M0 classification. Materials and methods Data were obtained from the Surveillance, Epidemiology, and End Results database (n = 4,217). A propensity score model was utilized to balance baseline covariates. Results Of the 4,217 included patients, 335 with ypTis-2N0M0 did not receive adjuvant chemotherapy. There were comparable cancer-specific survivals (CSS) between those undergoing adjuvant chemotherapy or not (log-rank test = 0.136, p = .712) in the overall sample. After propensity score matching, the cancer-specific survival did not differ between the chemotherapy and observation groups (log-rank test = 0.089, p = .765). Additionally, the Cox model did not demonstrate adjuvant chemotherapy as the prognostic factor, with hazard ratio = 0.95 (95% confidence interval 0.69-1.32) for CSS. Furthermore, the 10-year cumulative CSS was 78.7% and 79.4% between the chemotherapy and observation groups, indicating no significance, and no impact of adjuvant chemotherapy on survival was observed in different subgroups stratified by T stage, histological grade, histology, lymph nodes, and tumor size. Conclusion Patients with ypTis-2N0 rectal cancer did not benefit from adjuvant chemotherapy after preoperative radiology and radical surgery in this cohort study. These results provided new insight into the routine use of adjuvant chemotherapy for patients with rectal cancer with completed neo-adjuvant radiotherapy and curative surgery. Implications for practice Inconsistent recommendations for patients with rectal cancer receiving neo-adjuvant chemoradiation are offered by clinical guidelines. Adjuvant chemotherapy had no cancer-specific survival benefit, not only in the whole cohort, but also in the propensity score-matched cohort. A Cox model also confirmed adjuvant chemotherapy was not a significant prognostic factor in ypTis-2N0 rectal cancer. No survival benefit conferred by adjuvant chemotherapy was observed, regardless of whether T stage, histological type, grade, lymph nodes and tumor size varied.

Background/Aims: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Methods: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. Results: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. Conclusion: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

Arabidopsis lumen thiol oxidoreductase 1 (LTO1) - the At4g35760 gene product - was previously found to be related to reactive oxygen species (ROS) accumulation. Here, we show that ROS accumulated in a mutant Arabidopsis line (lto1-2, mutant of LTO1/AtVKOR) under osmotic stress at a higher level than that observed in wild-type and transgenic complemented plants of the lto1-2 mutant (lto1-2C, transgenic complemented plants of lto1-2). Because ROS accumulation in osmotic stress is triggered by abscisic acid (ABA), an ABA-responsive gene, Annexin 1 (AnnAt1), was selected to study the response. Osmotic stress or exogenous ABA can significantly upregulate the transcription of AnnAt1 in wild-type and lto1-2C plants. Only a slight change in the transcriptional abundance of AnnAt1 was observed under osmotic stress in the lto1-2 mutant, but exogenous ABA application could increase the expression of AnnAt1, which suggested that exogenous ABA had a partial complementation role. Because the transcription of AnnAt1 is regulated by ABRE (ABA-responsive elements) binding proteins (AREBs)/ABRE binding factors (ABFs), the expression of AREBs/ABFs was also analyzed. The transcription of AREBs/ABFs in the lto1-2 mutant was not induced by osmotic stress but was significantly upregulated by exogenous ABA, which significantly differs from the wild-type and lto1-2C plant responses. Similarly, the expression of another ABA-responsive gene, RD29B (responsive to desiccation stress gene 29B), in the lto1-2 mutant was also upregulated by exogenous ABA. The partial complementation of mutants by ABA indicated that the ABA signal transduction pathway was not significantly affected in the lto1-2 mutant. Taken together, these results suggest that LTO1 is involved in ABA-mediated response to osmotic stress, possibly by affecting the biosynthesis of endogenous ABA.

Background Crypt base cells are candidates for intestinal epithelial stem cells (ISC). But limited progress has been made concerning the modulation of stem cells. DACH1 is upregulated in LGR5+ ISC cells with stemness maintenance. Hence, we postulated that DACH1 may serve as a putative modulator of intestine stem cells leading to carcinogenesis. Methods We established colon normal, adenomas and cancers organoids, which supported stem cell proliferation and undifferentiation in vitro. A stable and efficient culture system for colon epithelial crypts and tumor organoids was use to facilitate investigation of the dynamics and factors affecting colon stem cell niche and carcinogenesis. Results We showed that in the mouse and human intestine, DACH1 was expressed in discrete crypt base. In colorectal cancer, DACH1 expression became widespread, with increased expression and nuclear localization at all stages. ShRNA-mediated inhibition of DACH1 in colon cancer cells inhibited colony formation in vitro and tumor growth in vivo through affecting cancer stem cell signatures. What is more, DACH1 stimulated both colonosphere formation and tumor organoid formation in vitro. Mechanistic characterization indicated that DACH1 recruited and interacts with SMAD4 to suppress BMP signaling pathway. Eventually, DACH1 induced stemness of organoids through BMP-mediated transcriptional increasing of a large number of stem cell signature genes, including Notch1, Msi-2 and Sox9. Here we provided evidence for an essential role of DACH1 in inducing stem cell self-renewal through direct upregulating stem cell signature genes. In detail, DACH1 was shown by microarray analyses to repress BMP induction of Smad signaling, then DACH1 binding to Smad4 was required for repression of Smad signaling Conclusions In conclusion, our findings illustrate an essential role of DACH1 signaling in inducing stem cell expansion during intestinal homeostasis and tumor development. This study also provided a mechanistic insight into the function of DACH1 in maintaining stem cell self-renewal via Smad4. Legal entity responsible for the study San-Jun Cai. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

There is disagreement about the prognostic value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients who have stage I-III colorectal cancer. Therefore, we investigated the relationship between preoperative serum CEA and CA19-9 levels and clinical outcome in patients with this disease.The study included 724 patients who had received radical resection for stage I-III colorectal cancer in Fudan University Shanghai Cancer Center. We retrospectively investigated the relationship between patients' characteristics and survival, using univariate and multivariate analyses. In multivariate analysis, factors found significant in the univariate analysis were compared with patients' outcomes.In univariate analysis, differentiation (P0.001), depth of invasion (P0.001), number of lymph node metastases (P0.001), and elevated levels of CEA (P0.001) and CA19-9 (P0.001) were closely correlated with patients' survival. In multivariate analysis, the number of lymph node metastases (P0.001), preoperative CA19-9 (P = 0.015) and CEA (P = 0.028) values, differentiation (p = 0.040) and depth of invasion (p = 0.039) were independent prognostic factors for survival.Preoperative CA19-9 and CEA have independent prognostic values in stage I-III colorectal cancer. Elevation of and both CEA and CA19-9 values predicted the worst outcome.

The objective of the article was to design a novel timed and controlled release osmotic pump (TCOP) containing atenolol as an active pharmaceutical ingredient and compare with a bilayer-core osmotic pump (BCOP) of atenolol. Different from BCOP, a modulating barrier was added to delay the drug release and obtain desired lag time (Tlag). The influences of the amount of pore-forming agent and modulating barrier, coating weight gain on the lag time (Tlag) and drug release rate (Rt) of TCOP were investigated. The central composite design-response surface methodology (RSM) was applied to optimize the formulation. Rhodamine B was added to modulating barrier to determine the release process of modulating barrier. A method used to correct the release profiles with a certain lag time by ΔTlag and interpolating was applied to compare TCOP with BCOP. Tlag was directly proportional to the amount of modulating barrier and coating weight gain, but inversely related to the amount of pore forming agent, which were contrary to the effects on Rt. The optimal formulation including 60 mg PEO WSR N80, 3 g PEG 4000 and 6% coating weight gain could obtain a 3.59-h Tlag. According to the release of Rhodamine B, the modulating barrier was completely pushed out at ∼5.0 h, longer than 3.59 h, therefore, atenolol along with remaining modulating barrier was released together between 3.59 and 5.0 h. By comparing with BCOP, the release profiles subtracting the part of lag time had no significant difference, yet Rt of TCOP presented a slight decrease.

Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial response of patients to these regimes and the severe peripheral neuropathy toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for oxaliplatin sensitivity to select suitable patients who benefit from these treatments. In present work, 21 CRC cell lines with different sensitivities to oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell lines were correlated to their response to oxaliplatin. Bioinformatics analysis suggested that expression of 58 genes was correlated, negatively or positively, to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly enriched in small molecules biochemistry, Wnt/β-catenin signaling and EMT pathways. The latter two pathways were predicted to be activated in oxaliplatin-resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their expression levels were actually closely correlated to their response to oxaliplatin, in line with the biocomputation prediction. Taken together, our work might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines and therapeutic targets for combinational therapy with oxaliplatin.

By using open-top chamber (OTC) and the techniques of dendrochronology, this paper studied the growth of Pinus armandii under elevated ozone, and explored the evolution dynamics and adaptation mechanisms of typical forest ecosystems to ozone enrichment. Elevated ozone inhibited the stem growth of P. armandii significantly, with the annual growth of the stem length and diameter reduced by 35.0% and 12.9%, respectively. The annual growth of tree-ring width and the annual ring cells number decreased by 11.5% and 54.1%, respectively, but no significant change was observed in the diameter of tracheid. At regional scale, the fluctuation of ozone concentration showed significant correlation with the variation of local vegetation growth (NDVI).

Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). Although irinotecan showed significant survival advantage for patients, a relatively low response rate and severe adverse effects demonstrated the urgent need for biomarkers searching to select the suitable patients who can benefit from irinotecan-based therapy and avoid the adverse effects. In present work, the irinotecan response (IC50 doses) of 20 CRC cell lines were correlated with the basal expression profiles investigated by RNA-seq to figure out genes responsible for irinotecan sensitivity/resistance. Genes negatively or positively correlated to irinotecan sensitivity were given after biocomputation, and 7 (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, and RNMT) of them were validated in two CRC cell lines by quantitative real-time PCR, several of these 7 genes has been proposed to promote cancer cells proliferation and hence may confer CRC cells resistance to irinotecan. Our work might provide potential biomarkers and therapeutic targets for irinotecan sensitivity in CRC cells.

The thylakoid protein LTO1/AtVKOR-DsbA is recently found to be an oxidoreductase involved in disulfide bond formation and the assembly of photosystem II (PSII) in Arabidopsis thaliana. In this study, experimental evidence showed that LTO1 deficiency caused severe photoinhibition which was related to the xanthophyll cycle and D1 protein degradation. The lto1-2 mutant was more sensitive to intense irradiance than wild type. When treated with different concentrations of dithiothreitol (DTT), an inhibitor of violaxanthin de-epoxidase (VDE) in the xanthophyll cycle, there was a larger reduction in NPQ in the wild type than in the lto1-2 mutant under high irradiance, indicating that lto1-2 had a lower sensitivity to DTT gradients than did the wild type. Zeaxanthin in the xanthophyll cycle, which participates in the thermal dissipation of excess absorbed light energy, was much less active in lto1-2 than in the wild type under intense light levels, and the de-epoxidation state of the xanthophyll cycle was consistent with the susceptibility of NPQ. Together these observations indicated that aggravated photoinhibition in lto1-2 was related to a reduction in xanthophyll cycle-associated energy dissipation. When D1 protein synthesis was suppressed by an inhibitor of chloroplast protein synthesis (streptomycin sulfate), the levels of D1 protein decreased more in the lto1-2 mutant than in the wild type when exposed to intense light levels, implying that a deficiency in LTO1 accelerated the degradation of D1 and thus affected D1 turnover. Transgenic complementation of plants with lto1-2 ultimately allowed for the recovery of the photoinhibition properties of leaves.

To evaluate the clinical effectiveness of three localization methods, including methylene blue, metal clips and intraoperative colonoscopy in laparoscopic colorectal surgery.A retrospective analysis was performed to review the clinical data of 64 patients who underwent the laparoscopic colorectal operations in Cancer Hospital of Fudan University from December 2009 to June 2012. Three methods of tumor localization were used perioperatively, including 23 cases of methylene blue, 20 of metal clips and 21 of colonoscopy.Operations were successfully performed in this cohort and there were no deaths or complications. In methylene blue group, intraoperative colonoscopy was performed in two cases because of the inability to visualize blue dye on the serosal surface of the intestinal wall, another 2 cases were converted to open operation because of methylene blue diffusion and inability to identify resection margin. Intraoperative colonoscopic localization was required for 3 cases of sigmoid colon or upper rectal tumor because of inaccurate tumor localization by metal clips. Poor operative exposure due to obvious bowel distension prompted the conversion to open surgery in 2 cases of colonoscopy localization group, and the accurate position of the lesion was not found in another 2 cases due to long pedunculated adenoma.Colorectal tumor can be localized effectively by endoscopic methylene blue tattooing at a maximum of 2 tumors before operation and the method of 4-point positioning can significantly improve the accuracy of colorectal tumor localization. Tumor localization preoperatively on the day of surgery by metal clip is accurate for the right or left colon cancer. Intraoperative colonoscopy can localize tumor accurately and rapidly for rectosigmoid or descending tumor, and the incidence of bowel distension can be significantly reduced. Localization method should be considered according to the tumor location and surgical procedure.

To study the in situ intestinal absorption kinetics of flrubiprofen in rats, the absorption of flurbiprofen in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC. The effects of drug concentration on the intestinal absorption were investigated. The K(a) and P(app) values of flurbiprofen in the small intestine and colon had no significant difference (P0.05). Drug concentration (4.0, 10.0 and 16.0 mg x L(-1)) had no significant influence on the K(a) values (P0.05). However, when concentration was 4.0 mg x L(-1) and 10.0 mg x L(-1), significant effect on the P(app) values (P0.05) was found, but significant effect on the P(app) values was not shown between 10.0 mg x L(-1) and 16.0 mg x L(-1) (P0.05). The K(a) and P(app) values of flurbiprofen on the perfusion flow rate had significant difference (P0.05). Flurbiprofen could be absorbed at all segments of the intestine in rats and had no special absorption window. The absorption of flurbiprofen complies with the facilitated diffusion in the general intestinal segments, and accompany with the cytopsistransport mechanism probably. The perfusion flow rate had significant effect on the K(a) and P(app).

To explore the relationship between CpG island methylator phenotype(CIMP) and genetic instability in sporadic colorectal cancer(SCRC).Seventy-one SCRC patients were enrolled in this study. Promotor methylation status of five genes including P14(ARF ), hMLH1, P16(INK4a), MGMT and MINT1 was detected with methylation specific PCR to confirm CIMP. Microsatellite instability (MSI) status was evaluated with two microsatellite loci of BAT25 and BAT26, and the ploidy was detected with flow cytometry. The association between CIMP and MSI as well as chromosomal instability(CIN) was examined.The positive rates of CIMP, MSI and aneuploidy were 21.1% (15/71), 9.9% (7/71) and 73.5% (50/68) respectively. The positive rate of MSI in positive CIMP patients was higher than that in negative CIMP ones, but the difference was not significant (20.0% vs 7.1%,P=0.158). The positive rate of MSI was 57.1% in patients with hMLH1 gene promotor hypermethylation, which was significantly higher than that (4.7%) in patients without hMLH1 gene promotor hypermethylation (P=0.001). SCRCs with positive CIMP displayed significant inclination of diploidy (P=0.003). The positive rate of diploidy among SCRCs with CIMP was 61.5% while only 18.2% of cases without CIMP demonstrated diploid.SCRCs with positive CIMP are significantly more likely to be diploid. Simultaneous multiple genes hypermethylation represented by CIMP may be an epigenetic mechanism competing with the genetic mechanism of CIN.