Nickel-Catalyzed Reductive Amidation of Aryl Fluorosulfates with Isocyanates: Synthesis of Amides via C-O Bond Cleavage.

With the assistance of nickel as catalyst, 2,2'-bipyridine (bpy) as ligand, and manganese as reducing metal, the reductive amidation of isocyanates with readily accessible aryl fluorosulfates could be successfully accomplished. The reactions proceeded effectively via C-O bond activation in DMF at room temperature, enabling the facile synthesis of a range of structurally diverse amides in moderate to high yields with broad functionality compatibility. In addition, the synthetic usefulness of the method was further demonstrated by applying the reaction in scale-up synthesis and the late-stage functionalization of complex molecules with biological activities.

Variation in the physiological response of adult worker bees of different ages (Apis mellifera L.) to pyraclostrobin stress.

The social division of labor within the honeybee colony is closely related to the age of the bees, and the age structure is essential to the development and survival of the colony. Differences in tolerance to pesticides and other external stresses among worker bees of different ages may be related to their social division of labor and corresponding physiological states. Pyraclostrobin was widely used to control the fungal diseases of nectar and pollen plants, though it was not friend to honey bees and other pollinators. This work aimed to determine the effects of field recommended concentrations of pyraclostrobin on the activities of protective and detoxifying enzymes, on the expression of genes involved in nutrient metabolism, and immune response in worker bees of different ages determined to investigate the physiological and biochemical differences in sensitivity to pyraclostrobin among different age of worker bees. The result demonstrates that the tolerance of adult worker bees to pyraclostrobin was negatively correlated with their age, and the significantly reduced survival rate of forager bees (21 day-old) with continued fungicide exposure. The activities of protective enzymes (CAT and SOD) and detoxifying enzymes (CarE, GSTs and CYP450) in different ages of adult worker bees were significantly altered, indicating the physiological response and the regulatory capacity of worker bees of different ages to fungicide stress was variation. Compared with 1 and 8 day-old worker bees, the expression of nutrient-related genes (ilp1 and ilp2) and immunity-related genes (apidaecin and defensin1) in forager bees (21 day-old) was gradually downregulated with increasing pyraclostrobin concentrations. Moreover, the expression of vitellogenin and hymenoptaecin in forager bees (21 day-old) was also decreased in high concentration treatment groups (250 and 313 mg/L). The present study confirmed the findings of the chronic toxicity of pyraclostrobin on the physiology and biochemistry of worker bees of different ages, especially to forager bees (21 day-old). These results would provide important physiological and biochemical insight for better understanding the potential risks of pyraclostrobin on honeybees and other non-target pollinators.

Resveratrol improved the spatial learning and memory in subclinical hypothyroidism rat induced by hemi-thyroid electrocauterization.

The major purpose of this study was to investigate the effect of resveratrol (RES) on the spatial learning and memory ability in subclinical hypothyroidism (SCH) rat model and the potential mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization and the activity of hypothalamus-pituitary-thyroid (HPT) axis was detected. The spatial learning and memory ability was tested using Morris water maze (MWM) and Y-maze. The protein expressions of synaptotagmin-1 (syt-1) and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured via western blot. The results showed that SCH rat model was successfully duplicated. The SCH rats showed impaired learning and memory in the behavioral tests. However, these changes were reversed by the treatment of RES (15mg/kg) and levothyroxine (LT4). Moreover, RES treated rats exhibited reduced plasma TSH level and hypothalamic thyrotropin releasing hormone (TRH) mRNA expression, which suggested that the imbalance of HPT axis in the SCH rats could be reversed by RES treatment. Furthermore, RES treatment up-regulated the protein levels of syt-1 and BDNF in hippocampus. These findings indicated an amelioration effect of RES on the spatial learning and memory in the SCH rats, the mechanism of which might be involved with its ability of modifying the hyperactive HPT axis and up-regulating the hippocampal hypo-expression of syt-1 and BDNF.

Field recommended concentrations of pyraclostrobin exposure disturb the development and immune response of worker bees (Apis mellifera L.) larvae and pupae.

The strobilurin fungicide pyraclostrobin is widely used to prevent and control the fungal diseases of various nectar and pollen plants. Honeybees also directly or indirectly contact this fungicide with a long-term exposure period. However, the effects of pyraclostrobin on the development and physiology of Apis mellifera larvae and pupae during continuous exposure have been rarely known. To investigate the effects of field-realistic concentrations of pyraclostrobin on honeybee survival and development, the 2-day-old larvae were continuously fed with different pyraclostrobin solutions (100 mg/L and 83.3 mg/L), and the expression of development-, nutrient-, and immune-related genes in larvae and pupae were examined. The results showed that two field-realistic concentrations of pyraclostrobin (100 and 83.3 mg/L) significantly decreased the survival and capped rate of larvae, the weight of pupae and newly emerged adults, and such decrease was a positive correlation to the treatment concentrations. qPCR results showed that pyraclostrobin could induce the expression of Usp, ILP2, Vg, Defensin1, and Hymenoptaecin, decrease the expression of Hex100, Apidaecin, and Abaecin in larvae, could increase the expression of Ecr, Usp, Hex70b, Vg, Apidaecin, and Hymenoptaecin, and decreased the expression of ILP1, Hex100 and Defensin1in pupae. These results reflect pyraclostrobin could decrease nutrient metabolism, immune competence and seriously affect the development of honeybees. It should be used cautiously in agricultural practices, especially in the process of bee pollination.

Experimental demonstration of probabilistic quantum cloning.

The method of quantum cloning is divided into two main categories: approximate and probabilistic quantum cloning. The former method is used to approximate an unknown quantum state deterministically, and the latter can be used to faithfully copy the state probabilistically. Thus far, many approximate cloning machines have been experimentally demonstrated, but probabilistic cloning remains an experimental challenge, as it requires more complicated networks and a higher level of precision control. In this work, we design an efficient quantum network with a limited amount of resources and perform the first experimental demonstration of probabilistic quantum cloning in a NMR quantum computer. In our experiment, the optimal cloning efficiency proposed by Duan and Guo [Phys. Rev. Lett. 80, 4999 (1998)] is achieved.

Technical Note: A deep learning-based autosegmentation of rectal tumors in MR images.

PURPOSE: Manual contouring of gross tumor volumes (GTV) is a crucial and time-consuming process in rectum cancer radiotherapy. This study aims to develop a simple deep learning-based autosegmentation algorithm to segment rectal tumors on T2-weighted MR images. MATERIAL AND METHODS: MRI scans (3T, T2-weighted) of 93 patients with locally advanced (cT3-4 and/or cN1-2) rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were enrolled in this study. A 2D U-net similar network was established as a training model. The model was trained in two phases to increase efficiency. These phases were tumor recognition and tumor segmentation. An opening (erosion and dilation) process was implemented to smooth contours after segmentation. Data were randomly separated into training (90%) and validation (10%) datasets for a 10-folder cross-validation. Additionally, 20 patients were double contoured for performance evaluation. Four indices were calculated to evaluate the similarity of automated and manual segmentation, including Hausdorff distance (HD), average surface distance (ASD), Dice index (DSC), and Jaccard index (JSC). RESULTS: The DSC, JSC, HD, and ASD (mean ± SD) were 0.74 ± 0.14, 0.60 ± 0.16, 20.44 ± 13.35, and 3.25 ± 1.69 mm for validation dataset; and these indices were 0.71 ± 0.13, 0.57 ± 0.15, 14.91 ± 7.62, and 2.67 ± 1.46 mm between two human radiation oncologists, respectively. No significant difference has been observed between automated segmentation and manual segmentation considering DSC (P = 0.42), JSC (P = 0.35), HD (P = 0.079), and ASD (P = 0.16). However, significant difference was found for HD (P = 0.0027) without opening process. CONCLUSION: This study showed that a simple deep learning neural network can perform segmentation for rectum cancer based on MRI T2 images with results comparable to a human.

Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/ß-Catenin Pathway.

Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 µg/kg for 16 days. The rats' plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/ß-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3ß (p-GSK3ß)/GSK3ß and protein levels of p-GSK3ß, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-ß-catenin (p-ß-catenin)/ß-catenin and expression of GSK3ß in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/ß-catenin pathway.

Depression-like Behavior Induced by Nesfatin-1 in Rats: Involvement of Increased Immune Activation and Imbalance of Synaptic Vesicle Proteins.

Depression is a multicausal disorder and has been associated with metabolism regulation and immuno-inflammatory reaction. The anorectic molecule nesfatin-1 has recently been characterized as a potential mood regulator, but its precise effect on depression and the possible mechanisms remain unknown, especially when given peripherally. In the present study, nesfatin-1 was intraperitoneally injected to the rats and the depression-like behavior and activity of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated. The plasma concentrations of nesfatin-1, interleukin 6 (IL-6), and C-reactive protein (CRP); and the hypothalamic expression levels of nesfatin-1, synapsin I, and synaptotagmin I mRNA were evaluated in nesfatin-1 chronically treated rats. The results showed that both acute and chronic administration of nesfatin-1 increased immobility in the forced swimming test (FST), and resulted in the hyperactivity of HPA axis, as indicated by the increase of plasma corticosterone concentration and hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Moreover, after chronic nesfatin-1 administration, the rats exhibited decreased activity and exploratory behavior in the open field test (OFT) and increased mRNA expression of synapsin I and synaptotagmin I in the hypothalamus. Furthermore, chronic administration of nesfatin-1 elevated plasma concentrations of IL-6 and CRP, which were positively correlated with despair behavior, plasma corticosterone level, and the hypothalamic mRNA expression of synapsin I and synaptotagmin I. These results indicated that exogenous nesfatin-1 could induce the immune-inflammatory activation, which might be a central hug linking the depression-like behavior and the imbalanced mRNA expression of synaptic vesicle proteins in the hypothalamus.

Nesfatin-1, a potent anorexic agent, decreases exploration and induces anxiety-like behavior in rats without altering learning or memory.

The anorectic neuropeptide nesfatin-1 has recently been characterized as a potential mood regulator, but the accurate effect of nesfatin-1 on anxiety and learning and memory behavior and the possible mechanisms remains unknown. In the present study, to test the hypothesis that nesfatin-1 might affect the anxiety-like and learning and memory behaviors in rats via ERK/CREB/BDNF pathway, nesfatin-1 was administered intraperitoneally to rats with the doses (10, 20, 40µg/kg), and the behavioral performance was tested using the open field task, the Morris water maze (MWM), and the Y maze. Moreover, the protein expression of brain-derived neurotrophic factor (BDNF), total and phosphorylated-ERK in the hippocampus and the prefrontal cortex (PFC) were evaluated. The results showed that chronic administration of nesfatin-1 could decrease the moving distance, the duration in the center, and the frequencies of rearing and grooming in the open field task, decrease the moving distance, frequency, and the preference index of new arm in the Y maze, although there was no significant difference of the performance in the MWM task among groups. Furthermore, 3 weeks' consecutive administration of nesfatin-1 resulted in the decrease of protein expression of BDNF and phosphorylated-ERK in the hippocampus and the PFC. These results provided evidence that exogenous nesfatin-1 could decrease exploration and induce anxiety-like behavior in rats, the mechanism of which might be related to the reduced protein expression of BDNF and phosphorylated-ERK in the hippocampus and the PFC.

Acute, but not chronic, stress increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats.

Nesfatin-1, a newly discovered satiety peptide, has recently been reported to be involved in the stress response. Stress-induced expression of nesfatin-1 has been reported and few studies focus on its expression in the hypothalamus, which is the center of the stress response. To test our hypothesis that peripheral and hypothalamic nesfatin-1 overexpression should play an important role in the stress response and the associated hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis, acute stress (AS) was induced using water avoidance stress (WAS), and chronic unpredictable mild stress (CUMS) was also induced using 3 consecutive weeks of 7 different stressors. The behavior of CUMS rats was evaluated by an open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). The activity of the HPA axis was detected by measurement of the plasma corticosterone concentration and hypothalamic mRNA expression of corticotropin-releasing-hormone (CRH). The plasma concentration and hypothalamic mRNA expression of nesfatin-1 were measured with an enzyme-linked immunosorbent assay (ELISA) and real-time fluorescent quantitative PCR, respectively. The results showed that both AS and CUMS increased the plasma corticosterone concentration and hypothalamic CRH mRNA expression. Depression-like behavior was induced in CUMS rats, as indicated by a decreased movement distance, frequency of rearing and grooming in the OFT, and sucrose preference index and increased immobility in the FST. Moreover, the AS rats showed increased plasma concentration and hypothalamic mRNA expression of nesfatin-1, which were positively correlated with the plasma corticosterone concentration and hypothalamic CRH expression, respectively. These results indicated that acute stress, but not chronic stress, increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats.

Human papillomavirus as an independent predictor in oral squamous cell cancer.

AIM: There is an increasing evidence for the role of high risk human papillomavirus (HPV) in the pathogenesis of oral squamous cell carcinoma (OSCC). The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC. METHODOLOGY: Fifty-two patients with OSCC were followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified in formalin-fixed, paraffin-embedded tumor specimens by nested PCR with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype was determined by direct DNA sequencing. Association between the HPV status and risk factors for cancer as well as tumor-host characteristics were analyzed. Survival curves were calculated by the Kaplan-Meier method and analyzed using the log-rank test. RESULTS: HPV was found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%, HPV6 for 3.9% and HPV11 for 1.8%. No infection with more than one HPV genotype was detected. HPV infection was significantly associated with poor histological grade, TNM stage I-II, alcohol usage and no smoking status. Multivariate analysis showed that HPV had an independent prognostic effect on the overall survival after adjusting other confounding factors such as histological grade, TNM stage and tobacco usage. The presence of HPV was significantly correlated with a better survival in patients with OSCC. CONCLUSION: HPV infection can act as an independent predictor for the survival and prognosis of OSCC.

Quantum adiabatic algorithm for factorization and its experimental implementation.

We propose an adiabatic quantum algorithm capable of factorizing numbers, using fewer qubits than Shor's algorithm. We implement the algorithm in a NMR quantum information processor and experimentally factorize the number 21. In the range that our classical computer could simulate, the quantum adiabatic algorithm works well, providing evidence that the running time of this algorithm scales polynomially with the problem size.