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Effective and comprehensive evaluation of cold stress is critical for healthy dairy cow breeding in the winter. Previous studies on dairy cow cold stress have considered thermal environmental factors but not physiological factors or air quality. Therefore, this study aimed to propose a multilevel fuzzy comprehensive evaluation (FCE) method for cold stress in dairy cows based on the analytic hierarchy process (AHP) and a genetic algorithm (GA). First, the AHP was used to construct an evaluation index system for cold stress in dairy cows from 3 dimensions: thermal environment (temperature, relative humidity, wind speed, and illumination), physiological factors (respiratory rate, body surface temperature), and air quality [NH

膜解剖理论是近年在胃肠外科日渐兴起的一种新的肿瘤手术理论，但其本质与范畴仍存在较多争议。对于很多年轻医生而言，膜解剖更像是一种理念，在指导手术实战操作中仍存在很多困难。本文从笔者手术团队开展膜解剖理念应用的临床经验出发，阐述对膜解剖的再认识与思考，重点分享笔者对传统膜解剖的狭义膜解剖、广义膜解剖以及膜解剖的膜界二象性等理论延伸的理解。.

Negative ion beam source test equipment, currently under construction at Institute of Plasma Physics, Chinese Academy of Sciences, is a prototype of a radio-frequency (RF) ion source for neutral be...

Reliability tests, such as Time-Dependent Dielectric Breakdown (TDDB), High-Temperature Operating Life (HTOL), Hot Carrier Injection (HCI), etc., is required for the lifetime prediction of an integrated circuit (IC) product. Those reliability tests are more stringent and complex especially for automotive Complementary Metal–Oxide–Semiconductor (CMOS) devices, this because it involves human lives and safety. In foundries failure analysis (FA), Transmission Electron Microscopy (TEM) analysis often required in order to provide insights into the defect mechanisms and the root cause of the reliability tests. In this paper, application of high resolution Nano-probing Electron Beam Absorbance Current (EBAC), Nano-probing active passive voltage contrast (APVC), and TEM with Energy Dispersive X-Ray Spectroscopy (EDX) to identify the failing root cause of Inter- Poly Oxide (IPO) TDDB failure on an automotive grade Non- Volatile Memory (NVM) device was investigated. We have successfully demonstrated that TEM analysis after Nanoprobing EBAC/APVC fault isolation is an effective technique to reveal the failure root cause of IPO breakdown after reliability stresses.

Perylene diimide derivatives (PDIs) with different substituents in the bay positions (Un-PDI, DFPDI and THBPDI) were chosen in this report to investigate the effect of potential on the reduction of PDIs through base (hydrazine, 1,2-ethanediamine and triethylamine)-driven keto-enol anion tautomerism. The reduction potentials (PDI/PDI•–) of these compounds determined via cyclic voltammetry are –0.51, ‒0.34, and –0.098 V for Un-PDI, DFPDI, and THBPDI, respectively. The reduction of Un-PDI, DFPDI and THBPDI by hydrazine can produce corresponding radical anions and dianions, but the volume of hydrazine added at which the radicals started to appear is different and depends on their reduction potential. The similar phenomenon was observed using 1,2-ethylenediamine and triethylamine. However, only the radical anion was obtained even in a large excess of 1,2-ethanediamine or triethylamine. Moreover, the reduction of these PDIs with different bases added in the same amount was investigated, and the correlation with their basicity was shown.

Surgical site infection is one of the most common complications for patients after sacrectomy, which often accompanied by poor wound healing, sinus formation and serious metabolic disturbance.We tried to avoid the surgical site infection caused by feces during early period after surgery through early fasting and total parenteral nutrition (TPN) support, then compared the clinical results of these patients with other patients that received enteral nutrition (EN) early after sacrectomy.Forty-eight patients after sacrectomy (the level of sacrectomy above SThe p-value of total serum protein, albumin, serum alanine aminotransferase, total bilirubin at seventh day after sacrectomy between TPN group and EN group is0.0005. The p-value of hemoglobin at seventh day after sacrectomy between TPN group and EN group is 0.001. The p-value of total serum protein at fourteenth day after sacrectomy between TPN group and EN group is 0.003. The p-value of albumin and total bilirubin at fourteenth day after sacrectomy between TPN group and EN group is 0.001. The p-value of hemoglobin, serum alanine aminotransferase at fourteenth day after sacrectomy between TPN group and EN group is0.0005. The incidence of gastrointestinal complication and delay of apparition of feces in EN group were lower than that in TPN group (p=0.041, p0.0005). The incidence of surgical site infection, the time of incision healing and hospitalization in TPN group were lower than that in EN group (p=0.048, p=0.008, p0.0005).The method of fasting and supported by TPN during the early period after sacrectomy contribute to the incision healing, meanwhile, it shortens the hospitalization time and abates the incidence of complications in patients after sacrectomy.It is a comparative randomized study.High-powered prospective randomized trial.

A new series of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purine-8-caboxamide derivatives were designed, synthesized, and further evaluated for their antiproliferative activities on four human cancer cell lines (A549, MGC803, PC-3 and TE-1). The structure-activity relationships (SARs) studies were conducted through the variation in the two regions, which including position 8 and 9, of purine core. One of the compounds, 8, containing a terminal piperazine appendage with a carboxamide moiety at position 8 and phenyl group at position 9 of 6-chloro-8,9-dihydro-7H-purine core, showed the most potent antiproliferative activity and good selectivity between cancer and normal cells (IC50 values of 2.80 μM against A549 and 303.03 μM against GES-1, respectively). In addition, compound 8 could inhibit the colony formation and migration of A549 cells in a concentration-dependent manner, as well as induce the apoptosis possibly through the intrinsic pathway.

A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC50 value of 1.55 μM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR+) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC50 value of 8.48 and 3.29 μM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library.

ABCB1-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A series of pyrimidine-based hybrid molecules containing 1,2,3-triazole moiety were evaluated for their reversal activities against MDR. The majority of target compounds displayed moderate to great reversal potency. Among these compounds, compound 25 displayed the most potent reversal activity, about 7-fold more potent than Verapamil (VRP). Further mechanism studies revealed that compound 25 could obviously reverse paclitaxel (PTX) resistance in SW620/AD300 cells by increasing accumulation and extending maintenance of PTX. Our findings indicate that the 1,2,3-triazole-pyrimidine-based derivatives may serve as an interesting lead for the development of new potent and efficacious ABCB1-dependent MDR modulators.

本文报道一例66岁男性患者行胃癌根治术后出现经内镜证实的代胃空肠袢漏，经内镜下钛夹封闭漏口治疗后，恢复良好。.

Crataegus pinnatifida Bge. var. major N. is a time-honored herbal medicine and an important economic fruit that is processed into various foods. Cultivated fields are mostly situated in northern China. In August 2012, a fruit brown rot disease on mature plants was found in Fushun, Liaoning Province, China. This disease reduced the yield and the quality of fruits; the incidence of fruits affected in each tree was between 20% and 35%. The initial stage of infection was marked by regular or irregular light brown spots turning dark brown and gradually supporting many grey fluffy tufts of mycelium. At last, the lesions expanded, causing the fruits to become rotted or withered. The pathogen was isolated from infected fruits by a tissue isolation method (1) and cultured on potato dextrose agar (PDA) at 25°C under 12 h light/12 h dark for 7 days. The colonies reached 60 to 75 mm in diameter after 7 days and were pale green or pale yellow with a neat greyish white margin; the aerial mycelium sometimes formed annulations. The conidia were single, hyaline, lemon-shaped or oval, and 11.3 ± 1.4 (8.0 to 16.5) × 6.4 ± 0.8 (5.1 to 7.6) μm; sporulation was sparse and stromata that formed after 15 days were abundant, black, and spherical to elliptical in shape. Conidiophores were simple or branched, bearing a single conidium on the tip. The internal transcribed spacer (ITS) region of rDNA amplified with primers ITS1 and ITS4 was directly sequenced in both directions. The ITS1-5.8S-ITS2 sequence of rDNA was 100% identical to Monilinia yunnanensis (GenBank Accession No. HQ908788.1), which is distinguished from the closely related M. fructigena (AF150679.1) and M. polystroma (JX315717.1). The pathogen was identified as M. yunnanensis on the basis of morphological characteristics (2) and the ITS sequence of rDNA (2,3). Pathogenicity tests were performed on detached healthy fruits. Four fruits were wounded with a sterilized nail and inoculated by placing a PDA plug of mycelia on upper surfaces of the fruits. Another four fruits treated with sterile PDA plugs served as a control. Fruits were cultured in petri dishes with a 12-h photoperiod at 25°C and 90% relative humidity. The initial symptoms on inoculated fruits were observed after 5 days, while no symptoms showed on the controls. The pathogen was reisolated from the inoculated fruit and identified as M. yunnanensis by the above methods. While M. yunnanensis has been reported to cause brown rot on peach (2), to our knowledge, this is the first report of M. yunnanensis infecting C. pinnatifida Bge. var. major N. in China. References: (1) Z. D. Fang. Research Methods of Plant Disease, 1998. (2) M. J. Hu et al. Monilinia species causing brown rot of peach in China. PLoS ONE. Online publication. doi:10.1371/journal.pone.0024990, 2011. (3) G. C. M. van Leeuwen et al. Mycol. Res. 106:444, 2002.

Xanthium orientale subsp. italicum (Moretti) Greuter is an annual herbaceous plant in the Asteraceae family, native to North America. It was first found in Beijing, China, in 1991. Since then, it has spread into many provinces such as Heilongjiang, Jilin, Liaoning, Hebei, Shandong, Xinjiang, and so on. Furthermore, it has been listed as one of the dangerous quarantine weeds in China (4). This noxious invasive weed has a strong ability to acclimatize to new environments. X. orientale subsp. italicum can usually be found in alluvial flatlands, riverbanks, wastelands, roadsides, pastures, as well as farmlands. The presence of this plant decreases the native biodiversity and influences the production of agriculture and stockbreeding. In August 2013, a rust disease was first observed on X. orientale subsp. italicum in Dalian, Liaoning Province, northeast China. Various sized lesions were found on approximately one third of the leaves of each infected plant. These lesions were yellow in the early stage of infection; gradually the center of each lesion turned brown, and eventually the infected lesions became necrotic and ruptured. The small (on average 4 mm in diameter) and dark brown raised telia appeared in the center of the lesions on the lower leaf surface. The teliospores were brown, clavate, two-celled, and measured 42 to 58 × 12 to 21 μm. Teliospores had a conical top, constricted septa, and a persistent pedicel (22 to 70 μm in length). The walls of the teliospores were smooth, 0.8 to 1.2 μm thick at the side and 4 to 8 μm thick at the apex. The size, color, and morphology of the teliospores fit the description of Puccinia xanthii (1,3). A pathogenicity test was conducted by the method of detached leaf inoculation (2). We collected 48 healthy leaves from six individuals of X. orientale subsp. italicum plants, eight from each individual. Teliospores from disease samples were suspended to 1 × 105 spores per ml with sterile water and then smeared on 24 leaves (four per individual); the remaining leaves were inoculated with sterile water as control. Each of the leaves was put on a moist filter paper in a petri dish, and was cultured in a chamber with a 12-h photoperiod at 25°C. Seven days later, dark brown raised telia were observed on all inoculated leaves but not on control ones. The teliospores were removed from the sorus on inoculated leaves, and according to the morphology confirmed to be those of P. xanthii. The rust caused by P. xanthii has been documented in different hosts in many other countries such as Spain, France, Italy, former Yugoslavia, Australia, the United States, and South Africa. In addition, the rust fungus was found to infect X. orientale subsp. italicum in eastern Hungary (1). To our knowledge, this is the first report of P. xanthii attacking the invasive plant X. orientale subsp. italicum in China. It is important to study the potential of using this rust fungus as a biological control agent of X. orientale subsp. italicum. This work was supported by the Project of the National Natural Science Foundation of China (31270582). References: (1) I. Dávid et al. Plant Dis. 87:1536, 2003. (2) Z. D. Fang. Research Methods of Plant Disease, 1998. (3) J. A. Parmelee. Can. J. Bot. 47:1391, 1969. (4) F. H. Wan et al. Biological Invasion: Color Illustration of Invasive Alien Plants in China, 2012.

To explore anti-gastric cancer agents with high efficacy and selectivity, we report the design, synthesis and optimization of a novel series of 3-(2,6,9-trisubstituted-9H-purine)-8-chalcone derivatives starting from the compound PCA-15 reported by us previously. Most of the target compounds demonstrated significant antiproliferative effects on MGC803 cancer cell line, and more potent than the positive control (PCA-15 and 5-Fu). Among them, compound 6o was identified to be the most active compound against MGC803 cell line with an IC50 value of 0.84 μM. Additionally, high selectivity was also observed between cancer and normal cells (23.35 μM against GES-1). Further mechanism studies confirmed that compound 6o could inhibit colony formation and migration, induce the apoptosis of MGC803 cells through both the mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which were evidenced by the up-regulation of Bax, cleaved-caspase 9/3/8, cleaved PARP and down-regulation of Bcl-2. Our systematic studies implied a new scaffold targeting gastric cancer cells for further development of small-molecule compounds with improved potency and selectivity.

P-glycoprotein (ABCB1)-mediated multidrug resistance (MDR) has become a major obstacle in successful cancer chemotherapy, which attracted much effort to develop clinically useful compounds to reverse MDR. Here, we designed and synthesized a novel series of derivatives with a 5-cyano-6-phenylpyrimidine scaffold and evaluated their potential reversal activities against MDR. Among these compounds, 55, containing an acylurea appendage, showed the most potent activity in reversing paclitaxel resistance in SW620/AD300 cells. Further studies demonstrated 55 could increase accumulation of PTX, interrupt ABCB1-mediated Rh123 accumulation and efflux, stimulate ABCB1 ATPase activity, and especially have no effect on CYP3A4 activity, which avoid drug interaction caused toxicity. More importantly, 55 significantly enhanced the efficacy of PTX against the SW620/AD300 cell xenograft without obvious side effects for orally intake. Given all that, the pyrimidine-acylurea based ABCB1 inhibitor may be a promising lead in developing new efficacious ABCB1-dependent MDR modulator.

Granulocyte colony-stimulating factor (G-CSF) plays a role in regulating phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K/AKT) pathway, affecting cell proliferation and apoptosis, and inducing vascular endothelial growth factor (VEGF) expression. This study investigated the mechanism of G-CSF on angiogenesis and neural protection after intracerebral hemorrhage (ICH).The rats were divided into four groups, including sham, ICH, ICH+G-CSF, and ICH+G-CSF+LY294002 (PI3K/AKT signaling pathway specific inhibitor). Cerebral neurological dysfunction was tested by Garcia scoring. Cell apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Angiogenesis marker CD34 expression, PI3K/AKT signaling pathway, B-cell lymphoma-2 (Bcl-2), and VEGF expressions were compared by IHC. Rat cerebral nerve RN-c cells were divided into four groups, including control, oxygen-glucose deprivation (OGD), OGD+G-CSF, and OGD+G-CSF+LY294002.Neurological dysfunction was more evident; CD34+ cell number, VEGF expression, and cell apoptosis significantly increased; phosphorylated AKT (p-AKT) and Bcl-2 levels markedly reduced in ICH group compared with sham group. G-CSF apparently up-regulated p-AKT and Bcl-2 expressions, attenuated cell apoptosis, and elevated CD34+ cell number. LY294002 significantly decreased p-AKT, Bcl-2, and VEGF expressions, and alleviated the cell apoptosis protective and angiogenesis effect induced by G-CSF. OGD treatment induced RN-c cell apoptosis, down-regulated p-AKT and Bcl-2 expressions, and enhanced the tube capacity of vascular endothelial cells (VEC). G-CSF markedly elevated p-AKT and Bcl-2 contents in RN-c cells, declined cell apoptosis, increased p-AKT and VEGF levels in VEC, and enhanced tube capacity.G-CSF enhanced PI3K/AKT signaling pathway activity, promoted Bcl-2 and VEGF expression, reduced nerve cell apoptosis, and enhanced tube capacity of VECs, which may be the mechanism of G-CSF in improving neurological function and angiogenesis after ICH.

To evaluate the mechanism of bone marrow mononuclear cells (BMMNCs) in reducing the oxidative stress after cerebral infarction through PI3K/AKT/NRF2 signaling pathway.96 healthy SD rats, which were 6-8-week old, weighting about 250-280 g, were selected for the study. The middle cerebral artery occlusion model (MCAO) was established in SD rats using the suture method. The rats were randomly divided into sham operation group, model group, BMMNCs group and PI3K inhibitor group. 24 rats in each group were selected. 200 μl phosphate-buffered saline (PBS) solution was injected into the caudal vein of the rats in the model group, 200 μl PBS solution containing 5×106 BMMNCs that obtained by gradient centrifugation was injected into the rats in the BMMNCs group, meanwhile, in the PI3K inhibitor group, LY294002 (10 mmol/L/kg) was injected into the lateral ventricle of the brain. After the 3d, 7d and 14d, the modified neurological severity scores (mNSS) were used to evaluate the neurological function. The volume of cerebral infarction was assessed by TTC staining, the VEGF, BDNF, TNF-α, IL-1β, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were detected by ELISA.The mNSS and the volume of cerebral infarction of the model group were significantly higher than those of the sham operation group (p0.05), while the mNSS and the volume of cerebral infarction of the BMMNCs group were lower than those of the model group, higher than those of the sham operation group (p0.05). The VEGF, BDNF, TNF-α, IL-1β, MDA, SOD and GSH-Px levels of the model group were significantly higher than those of the sham operation group (p0.05).BMMNCs can reduce the oxidative stress, apoptosis, and inflammatory reaction through PI3K/AKT/NRF2 signaling pathway, thus promoting the secretion of nerve and vascular cytokines, improving the neurological function and reducing the infarct scope.

The Rab protein family belongs to a superfamily of ras-like GTP-binding proteins. Rab proteins regulate many steps of membrane trafficking. In this study, three Rab family members, Rab5B, Rab6A, and Rab7, designated LvRab5B, LvRab6A, and LvRab7, were cloned from Litopenaeus vannamei. The full-length cDNA sequences of LvRab5B, LvRab6A, and LvRab7 were 1383, 873, and 767 nucleotides in length and they encoded proteins of 211, 212, and 205 amino acids, respectively. Using qRT-PCR, the mRNA expression levels of the three proteins were determined in the hepatopancreas of L. vannamei at different stages after infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus challenge. The results indicated that the mRNA expression levels of LvRab5B, LvRab6A, and LvRab7 were all significantly up-regulated after virus injection, suggesting that these genes may play essential roles in the immune response to viral infection in shrimp.

To study the structural and functional changes in mitochondria in astrocytes of the cerebral cortex of the rats in the simulated sepsis environment in vitro and the relationship between these changes and the biogenesis of mitochondria in astrocytes by establishing models of sepsis astrocytes.The structural and functional changes in mitochondria in astrocytes of the cerebral cortex of the rats were evaluated. The ultra structural changes in the mitochondria, astrocytes, and ultrathin sections, were observed with a transmission electron microscope. The expression of the regulatory factors related to biogenesis of mitochondria in astrocytes of the cerebral cortex of the rats was evaluated in various experimental groups. RT-PCR and Western blot were used to evaluate the expression of the regulatory factors related to biogenesis of mitochondria in astrocytes of the cerebral cortex of the rats. The "point grid method" was used to evaluate the volume density of the mitochondria in the astrocytes of the cerebral cortex of the rats in various experimental groups. The Western blotting was used to evaluate the role of fusion and fission of mitochondria in the astrocytes of the cerebral cortex of the rats in various experimental groups in regulating the expression of the protein-OPAI and DRPI.In the sepsis astrocyte models established by co-incubation of LPS and IFN-γ and astrocytes of the cerebral cortex of the rats, the mitochondria with a minor injury in the 6 h group (2.97± 0.92) increased significantly when compared with those in the 0 h group (1.08±0.95), 12 h group (1.70±1.01), and 24 h group (1.59±0.55) (p0.05); the concentration of adenosine triphosphate (ATP) in the astrocytes of the cerebral cortex of the rats in the 6 h, 12 h, and 24 h groups increased significantly when compared with that in the 0 h group (p0.05). PGC-1α mRNA, NRF-1 mRNA, NRF-2α mRNA, NRF-2β mRNA, and mitochondrial transcription factor A (TFAM) mRNA in the astrocytes of the cerebral cortex of the rats in the 6 h and 12 h groups increased significantly when compared with those in the 0 h group (p0.05); the concentration of TFAM mRNA (1.20±0.19) increased significantly when compared with that in the 0 h group (p0.05). The OPAI protein concentration (1.21±0.17:1.34±0.06) and DRPI protein concentration (1.04±0.05; 1.05±0.05) in the astrocytes of the cerebral cortex of the rats in the 12 h group (1.25±0.17), 24 h group (1.33±0.24), and 6 h group increased significantly when compared with that in the 0 h group (p0.05).The experimental sepsis conditions can cause a minor injury of the ultrastructure of the mitochondria in the astrocytes of the cerebral cortex of the rats. The biogenesis of the mitochondria in the astrocytes of the cerebral cortex of the rats was strengthened to cater for the increased demand for energy of the astrocytes under the sepsis conditions and finally recover the ultrastructure of the mitochondria with a minor injury. In response to the increased mitochondrial biogenesis, the activities of the mitochondrial fusion and fission of the astrocytes of the cerebral cortex of the rats were increased.

Histone lysine specific demethylase 1 (LSD1) plays an important role in epigenetic modifications, and aberrant expression of LSD1 predicts tumor progression and poor prognosis in human esophageal cancers. In this study, a series of LSD1 inhibitors were synthesized and proved to be highly potent against human esophageal squamous cell carcinoma (ESCC). Our data showed that these LSD1 inhibitors selectively suppressed the viability of esophageal cancer cell line (EC-109) bearing overexpressed LSD1. Among these, compound LPE-1 (LSD1 IC50=0.336±0.003μM) significantly suppressed proliferation, induced apoptosis, arrested cell cycle of EC109 cells at G2/M phase, and caused changes of the associated protein markers correspondingly. We also found that compound LPE-1 potently inhibited the migration and invasion of EC-109 cells. Docking studies showed that the cyano group formed hydrogen bonds with Val811 and Thr810. Additionally, the thiophene moiety formed arene-H interaction with Trp761 residue. In vivo studies showed that compound LPE-1 inhibited tumor growth of xenograft models bearing EC-109 without obvious toxicity. Collectively, our findings indicate that LSD1 may be a potential therapeutic target in ESCC, and compound LPE-1 could serve as a lead compound for further development for anti-ESCC drug discovery.