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Introduction: This study aimed to compare the accuracy of seven implantable collamer lens (ICL) implantation vault prediction formulae. Methods: We retrospectively analyzed 328 patients (328 eyes) who underwent ICL implantation and the prediction accuracy of seven formulae: NK, KS, WH, Luo, Zhu, Hun, and ZZ were compared. Moreover, the accuracy of the seven formulae for different ICL sizes was compared. The formulae were tested using mean absolute prediction error (MAE), median absolute prediction error (MedAE), prediction error (PE) percentages at ± 50 µm, ± 100 µm, ± 200 µm, and ± 300 µm, and Bland-Altman analysis. Results: The PE of the seven formulae were statistically significant (P < 0.001). The KS (101.00 µm) and WH formulae (116.65 µm) had the smallest MedAE, followed by the Luo (123.62 µm), NK (141.50 µm), Hun (152.68 µm), ZZ (196.00 µm) and Zhu formula (225.98 µm). The highest percentage of PE in the range of ± 300µm was 94.3% and 93% for the KS and WH formulae, respectively. Among the different ICL size groupings, the KS formula predicted the smallest MedAE for 12.1 mm and 12.6 mm, whereas the Luo and WH formulae predicted the smallest MedAE for 13.2 mm and 13.7 mm, respectively. Conclusions: The KS and WH formulae provided better outcomes by predicting the vault with higher accuracy than of the NK, Hun, Luo, ZZ, and Zhu formulae. Trial Registration: ChiCTR2200065501. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore the effects of the ciliary sulcus angle (CSA) on accurate prediction of the vault after phakic implantable collamer lens (EVO ICL Model V4c) using the KS formula. Methods: Patients were classified according to the size of CSA: group A, narrow angle (CSA < 30°); group B, normal angle (CSA = 30–90°); and group C, wide angle (CSA > 90°). Further, differences between the actual vault dimensions at 3 months postoperatively and the preoperatively predicted vault dimensions in the three groups were analyzed. Results: This study included 223 eyes of 223 individuals. In groups A–C, the difference in the preoperative vault dimensions of the three groups predicted with the KS formula was not statistically significant (P = 0.056). The actual vault dimensions at 3 months postoperatively were significantly different between the three groups (P < 0.001). Moreover, the difference between the actual and predicted vaults by the KS formula was statistically significant (P < 0.001). In the 3 months, after surgery, the percentages of patients with a low vault (< 250 μm) were 0%, 3%, and 29% in groups A, B, and C, respectively. Further, the percentages of patients with an ideal vault (250–750 μm) in the postoperative period were 66%, 84%, and 71% in groups A, B, and C, respectively. Finally, the percentages of patients with a high vault (> 750 μm) in the postoperative period were 34%, 13%, and 0% in groups A, B, and C, respectively. Notably, the distribution of the vault among the three groups was statistically significant (P < 0.001). Conclusion: The size of CSA significantly affects the predictiveness of the vault by the KS formula, with the most pronounced effect on the angles < 30° and > 90°. Therefore, CSA should be considered when selecting the lens size using the KS formula preoperatively. Clinical Trial Registration number: ChiCTR2200065501. [ABSTRACT FROM AUTHOR]

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3–6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7–15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light–dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.The Drosophila R8 photoreceptor separates signals for image perception and circadian photoentrainment by co-releasing histamine and acetylcholine, and this segregation is further established in the postsynaptic circuitry in the medulla. [ABSTRACT FROM AUTHOR]

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients. Combination of immune checkpoint inhibitors with anti-angiogenic targeted therapy has shown efficacy in some solid tumours. Here the authors report the results of a phase 2 trial of camrelizumab (anti-PD1) plus apatinib as a second-line or later-line treatment regimen in platinum-resistant (cohort 1) or PD-1 inhibitor-resistant (cohort 2) Recurrent/Metastatic Nasopharyngeal Carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Salt stress seriously impacts the plantation and productivity of global alfalfa (Medicago sativa). Previously, we genetically defined the M. sativa DROUGHT-INDUCED UNKNOWN PROTEIN 1 (MsDIUP1) as a drought tolerance gene of alfalfa. However, whether it is associated with salt tolerance needs to be explored. Results: In this study, we re-classified MsDIUP1 as a putative novel late embryogenesis abundant protein, and found its promoter activity was strongly induced by salt and ABA treatment. Heterologous overexpression of MsDIUP1 in Arabidopsis led to enhanced salt tolerance and ABA insensitivity, with a higher fresh weight, lateral root number, primary root length, and survival rate compared to the wild-type (WT) plants. Similarly, homologous overexpression of MsDIUP1 also enhanced the salt tolerance of alfalfa over-expression (OE) plants, accompanied by reduced oxidative damage, higher K+/Na+ ratio, increased osmoprotectant accumulation, and improved photosynthetic capacity relative to the WT plants. In reverse, disruption of MsDIUP1 expression caused a salt-hypersensitive phenotype of alfalfa RNA interference (RNAi) plants, with higher oxidative damage, less osmoprotectant accumulation, and lower photosynthetic pigment content than that of the WT. These physiological discoveries were in accordance with differential transcript profiles of the relevant genes associated with stress signaling, antioxidant defense, and osmotic adjustment in the salt-treated alfalfa WT, OE, and RNAi lines. Furthermore, we found that alfalfa OE plants showed no apparent alteration in their forage quality compared with the WT plants. Conclusions: Overall, these results reveal that MsDIUP1 improves plant salt tolerance via regulating stress signaling, antioxidant defense, ion homeostasis, osmotic adjustment, and photosynthesis. [ABSTRACT FROM AUTHOR]

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior. [ABSTRACT FROM AUTHOR]

Objectives: This study focused on developing and validating a nomogram to predict the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC) without distant metastasis based on their clinical characteristics, serum biomarkers, and presence of nasopharyngeal (NP) necrosis. Methods: This study included 9298 patients with NPC. Patients from January 2009 to December 2014 were randomly categorized into the training cohort and validation cohort A. Validation cohort B, whose data were collected from January 2015 to December 2017, was also included. OS was the primary endpoint of this study. Cox regression analysis was used to detect independent risk variables. Decision curve analysis, calibration curve, time-dependent receiver operating characteristic (ROC) curve, and concordance index (C-index) were used to evaluate the performance of the nomogram model. Results: A total of 267 patients developed NP necrosis after the first routine radiotherapy. After radiotherapy, patients with NP necrosis had significantly lower OS than other patients in all three cohorts (p < 0.001). Eleven factors, including NP necrosis, were involved in the nomogram, which had favorable discrimination and calibration with a C-index of 0.768 in the training cohort, 0.749 in validation cohort A, and 0.739 in validation cohort B. The nomogram exhibited a significantly larger area under the ROC curve for predicting OS than the TNM stage and Epstein-Barr virus (EBV) DNA (p < 0.001). Conclusion: Compared with the TNM system and EBV DNA, we established a nomogram model with an accurate prognostic prediction for patients with NPC, which might help with patient management in NPC. Key Points: • This study included 9298 patients with NPC, and 11 factors were involved in the final model. • The nomogram had a significantly higher C-index and area under the ROC curve than the TNM stage and EBV DNA. • We established the first nomogram model for NPC involving the occurrence of NP necrosis, which was valuable for providing individual counseling and clinical assessments. [ABSTRACT FROM AUTHOR]

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Charged metal-organic cages generally produce aggregates with various morphologies and different properties through the multiple supramolecular interactions in solution. Herein, a luminescent hexahedral metal-organic cage containing pyrene chromophores is successfully constructed through coordination-driven subcomponent self-assembly. The cage exhibits novel spontaneous aggregation in a dilute solution and time-dependent luminescence enhancement behavior during the subsequent incubation process. Dynamic light scatter (DLS) and transmission electron microscopy (TEM) results prove that the metal-organic cages can form blackberry-like aggregates in methanol dilute solution. Unexpectedly, the luminescent intensity of this system shows a linear increase with the extension of the incubation time in methanol, and this process is also reflected in the change in the quantum yield of the system (2% to over 80% after 5 days incubation time). Ultraviolet-visible (UV-vis), 1H nuclear magnetic resonance (1H NMR) and mass spectra show that metal-organic cages can stably exist in dilute solution. Time-depended DLS and TEM data reveal that the aggregates of metal-organic cages are gradually changed from the dense state to the loose one, which may involve the transition of the system from an energy unstable state to a stable one, probably leading to the unusual time-dependent luminescent property. This unique time-dependent luminescent cage aggregate can be potentially applied as a "supramolecular time meter". [ABSTRACT FROM AUTHOR]

We have prepared the metastable solid solutions of (Fe2O3)1−x(Al2O3)x (x = 0.25, 0.50, and 0.75) with the corundum-type structure through the mechanical alloying method and measured the low-temperature heat-capacity below 300 K using the Physical Property Measurement System (PPMS), which have not been measured so far since the solid solution is not available through the conventional synthesis procedure. The measured heat capacities exhibit similar general trends of temperature dependence with the pure α-Fe2O3 and α-Al2O3 listed in the JANAF thermodynamic table, while the measured values are a little higher than that of their weighted averages. This might be due to the defects or lattice distortion introduced at the preparation using the mechanical alloying method. Moreover, heat capacity anomaly was observed at low-temperature regions below 25 K, which grows larger and shifts toward the higher temperature with increasing aluminum substitution, which might be caused by the unexpected phase transition or point defects of cations. [ABSTRACT FROM AUTHOR]

The present study was designed to assess whether raised Serine protease inhibitor Kazal type 1 (SPINK1) expressions modulates angiogenesis. Human umbilical vein endothelial cells (HUVECs) exposed to SPINK1 were noted to exhibit raised expressions of interleukin-8 (IL-8) as well as VCAM-1 and ICAM-1 cell adhesion molecules in a dose-dependent manner. In co-culture system of HUVECs and Acute lymphoblastic leukemia (ALL) cells, SPINK1 exposure also resulted in enhanced endothelial cell motility and ALL cells trans-endothelial migration. High concentrations of SPINK1 caused in vitro cellular reorganization into tubes in Matrigel-cultured HUVECs and induced in vivo vascularization and brain infiltration of NOD/SCID ALL model mice. The further transcriptomic analysis indicated that SPINK1 treatment altered several biological processes of endothelial cells and led to activation of the MAPK pathway. This study is the first to determine the neovascularization effects of raised SPINK1. [ABSTRACT FROM AUTHOR]

The traditional Desai model fails to calculate the bearing capacity of a beam effectively, which could lead to its failure. In order to solve this problem successfully, a new RAV analysis model is proposed to analyze the stress behavior of steel fiber reinforced concrete beams. The vertical effect of steel fiber reinforced concrete (SFRC) beams is analyzed by means of a rod element simulation. The analysis results of the beam large displacement effect are determined using multi-stage displacements. Based on the above two physical quantities, the stress finite element equation is determined. According to the finite element equation, the reliability and response characteristics of the beam are analyzed, and a new RAV behavior analysis model is formulated. The results show that compared with the Desai model, the new RAV model can improve the accuracy of calculating the beam bearing capacity limit by about 40% under the conditions of high, medium and low nonlinear stresses. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. Methods: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. Results: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76–0.83) and 0.779 (95% CI, 0.74–0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. Conclusion: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging. [ABSTRACT FROM AUTHOR]

Objectives: The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods: A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions: This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients. [ABSTRACT FROM AUTHOR]

Background: Sigmoid colon cancer is a lethal disease and has a strong indication for surgery. Robotic-assisted surgery is one of the promising alternative treatment for this disease. Nowadays, the MicroHand S surgical system and the Da Vinci surgical system have been assembled in China. However, there is still no report to study the therapeutic effects of the two robotic-assisted surgical systems. Thus, the purpose of this study was to compare clinical and economic outcomes of patients with sigmoid colon cancer undergoing robot-assisted radical surgery via The MicroHand S or Da Vinci surgical system.Methods: The clinical data of 45 patients with sigmoid colon cancer undergoing the MicroHand S or Da Vinci robotic-assisted surgery at The Third Xiangya Hospital of Central South University from January 2017 to January 2019 were retrospectively analyzed.Results: Twenty-one patients received MicroHand S robotic-assisted radical surgery and 24 patients received Da Vinci robot-assisted radical surgery. No significant differences were observed in terms of operation time, number of lymph node harvested, blood loss, intestinal exhaust time, time of oral feeding resumption, volume of abdominal cavity 24-h drainage, hospital stay, complication and rate of conversion, removal time of drainage tube and catheter between MicroHand S and Da Vinci group. However, the MicroHand S group had significantly lower hospitalization costs (P = 0.002) and shorter time to get out of bed after surgery (P = 0.04). In addition, no recurrence and metastases were observed in both groups during the follow-up.Conclusions: In patients with sigmoid colon cancer, the Da Vinci surgical system did not show obvious clinical advantages compared to the MicroHand S surgical system in surgical outcomes. However, the MicroHand S surgical platform showed advantages in terms of the hospitalization costs and length of postoperative bedtime. The outcome of this study will probably result in a shift to the MicroHand S surgical system as treatment preference in China. [ABSTRACT FROM AUTHOR]

The phylogeny and systematics of cordycipitoid fungi have been extensively studied in the last two decades. However, systematic positions of some taxa in the family Cordycipitaceae have not yet been thoroughly resolved. In this study, a new phylogenetic framework of Cordycipitaceae is reconstructed using multigene (nrSSU, nrLSU, tef-1α, rpb1 and rpb2) sequence data with large-scale taxon sampling. In addition, ITS sequence data of species belonging to the Lecanicillium lineage in the family Cordycipitaceae are used to further determine their phylogenetic placements. Based on molecular phylogenetic data together with morphological evidence, two new genera (Flavocillium and Liangia), 16 new species and four new combinations are introduced. In the new genus Flavocillium, one new species F. bifurcatum and three new combinations previously described as Lecanicillium, namely F. acerosium, F. primulinium and F. subprimulinium, are proposed. The genus Liangia is built by the new species Lia. sinensis with Lecanicillium-like asexual morph, isolated from an entomopathogenic fungus Beauveria yunnanensis. Due to the absence of Paecilomyces hepiali, an economically and medically significant fungus, in the earlier phylogenetic analyses, its systematic position has been puzzling in both business and academic communities for a long time. Here, P. hepiali is recharacterized using the holotype material along with seven additional samples. It is assigned to the genus Samsoniella (Cordycipitaceae, Hypocreales) possessing Cordyceps-like sexual morph and Isaria-like asexual morph, and thus a new combination, namely S. hepiali is proposed. An additional nine new species in Samsoniella are described: S. alpina, S. antleroides, S. cardinalis, S. cristata, S. lanmaoa, S. kunmingensis, S. ramosa, S. tortricidae and S. yunnanensis. Four new species in Cordyceps are described: C. chaetoclavata, C. cocoonihabita, C. shuifuensis and C. subtenuipes. Simplicillium yunnanense, isolated from synnemata of Akanthomyces waltergamsii, is described as a new species. [ABSTRACT FROM AUTHOR]

The overseas oil and gas investment evaluation is one of the core tasks in overseas investment of oil and gas companies, among which risk evaluation and benefit evaluation are the most important. This paper sets forth transmission paths of risk factors to the investment benefit by identifying 14 overseas oil and gas investment risks in four categories. On the basis of the concept of risk compensation, different compensation mechanisms specific to each risk are designed. The risk and benefit are integrated objectively to develop a comprehensive evaluation model by correcting the recoverable reserve, adjusting benefit evaluation parameters such as investments on exploration and development, and compensating for the changes in risk factors with time through dynamic discount rate. Moreover, two cases studies, namely the evaluations of Project A in Sudan and comparison among Blocks A–G, are used to describe usage method and applicable scope of such evaluation model, respectively. According to the results, oil price is a key influencing factor for enterprise internal risk and industrial risk. Risk compensation reduces comprehensive benefit of overseas oil and gas investment and undermines the investment feasibility and priority of blocks. The research findings of this paper are free from the effects of some subject factors and avoid multi-objective decision making, and also avoid the undesired repeated calculation of risk factors. [ABSTRACT FROM AUTHOR]

Common vetch (Vicia sativa L.) is an important legume which is widely distributed around the world and an excellent forage and green manure crop, which could provide hay for pastoral areas in northwestern China, where feed is scarce during winter and early spring. However, there is currently limited information on genetic variation for some agronomic traits of common vetch, such as shattering rate, herbage yield, and seed yield. In our study, genotypic variation, phenotypic and genotypic correlations were estimated for 18 traits among 418 germplasms accessions of common vetch across 2 years, 2015 and 2016. All the traits evaluated had significant (P < 0.05) genotypic variation. Genotype-by-year interaction for all traits was significant (P < 0.05). The estimates of mean repeatability for the traits across 2 years ranged from 0.1316 for seed yield to 0.8571 for shattering rate. Three common vetch accessions groups were identified with low shattering rate, high herbage yield and high seed yield. Accession groups with a potential to breeding pools were also identified using pattern analysis. The results showed that the trait SR was significantly negatively correlated with DW and SY, which provided key information for common vetch breeding program with low shattering rate, high herbage yield and high seed yield. [ABSTRACT FROM AUTHOR]

Background: Pain due to oral mucositis (OM) is a major problem during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.Methods: We enrolled 56 NPC patients receiving CCRT and allocated them into two groups: moderate pain group (n = 27) and a severe pain group (n = 29) according to the degree of pain reported (moderate = numerical rating scale (NRS) score 4-6 or severe = NRS score 7-10) at initiation of controlled-release oxycodone (CRO) treatment.Results: Total dose of CRO was significantly higher in severe pain patients than in moderate pain patients (791.60 ± 332.449 mg vs. 587.27 ± 194.940 mg; P = 0.015). Moderate pain patients had significantly better quality of life (P = 0.037), lower weight loss (P = 0.030) and more active CCRT response (90.9% vs. 64.0%; P = 0.041). Although 24-h pain control rate was comparable in the two groups (85.2% vs. 86.2%; P = 0.508), the moderate pain group score eventually stabilized at ~ 2 vs. 3 in the severe pain group (P < 0.001); the titration time to reach bearable pain (NRS ≤ 3) was also significantly shorter in moderate pain patients (2.45 ± 0.60 days vs. 3.60 ± 1.98 days; P = 0.012). Incidence of adverse events was comparable in both groups.Conclusions: The study findings suggest that early introduction of low-dose CRO at the moderate pain stage could help reduce the total dose required, provide better pain control, improve quality of life, and enhance CCRT response. [ABSTRACT FROM AUTHOR]

The instabilities of a pendent viscous thin film underneath two corrugated ceilings are studied numerically and theoretically in comparison with the case of a flat wall. With the same initial interface perturbations, it is shown numerically that both the supercritical instability and the subcritical instability can be retarded by the in-phase corrugated ceilings. The lubrication approximation is used to explain the retardation effect of the corrugated ceiling on the supercritical instability of the pendant film, where the linear growth rate is revealed to be power three of the initial film thickness. [ABSTRACT FROM AUTHOR]

Furin is a proprotein convertase implicated in a variety of pathological processes including neurodegenerative diseases. However, the role of furin in neuronal plasticity and learning and memory remains to be elucidated. Here, we report that in brain-specific furin transgenic (Furin-Tg) mice, the dendritic spine density and proliferation of neural progenitor cells were significantly increased. These mice exhibited enhanced long-term potentiation (LTP) and spatial learning and memory performance, without alterations of miniature excitatory/inhibitory postsynaptic currents. In the cortex and hippocampus of Furin-Tg mice, the ratio of mature brain-derived neurotrophic factor (mBDNF) to pro-BDNF, and the activities of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) were significantly elevated. We also found that hippocampal knockdown of CREB diminished the facilitation of LTP and cognitive function in Furin-Tg mice. Together, our results demonstrate that furin enhances dendritic morphogenesis and learning and memory in transgenic mice, which may be associated with BDNF-ERK-CREB signaling pathway. [ABSTRACT FROM AUTHOR]

Previous phylogeographical studies of the Sino-Himalaya (SH) regions have mainly focused on seed plants from forest or alpine grassland habitats, whereas the flora of the subnival summits, especially the ferns, has largely been ignored. Here, we report on phylogeographical studies on Polystichum glaciale, a rare fern endemic to the subnival belt of the SH region. Based on cpDNA/nDNA sequences, strikingly rich genetic diversity was detected in P. glaciale. Combined with the lack of ‘isolation by distance’ and the major genetic differentiation among populations revealed by AMOVA, they collectively suggested that P. glaciale exhibited island-like population genetic structure. Phylogeographical structure with two genetic groups (N vs. S) was further identified in P. glaciale by the SAMOVA based on cpDNA data, of which the geographical pattern was mainly associated with the biogeographical boundary between the northern and southern Hengduan Mountains at 29°N latitude. We concluded that extremely complex topography of SH region and highly fragmented subnival habitat have played a critical role in shaping phylogeographical structure and genetic differentiation of P. glaciale. Mismatch distribution analyses and ecological niche modelling suggested P. glaciale has undergone north-westward retreat after the LGM. Predictions of its future distribution indicated the possibility of compression within suitable subnival habitats. We suggest in situ conservation should be urgently implemented to preserve this rare fern. Our results represent a first framework for a comprehensive understanding of the biogeographical history of fern species associated with the subnival belt of the SH region and the effects of historical events on its genetic architecture. [ABSTRACT FROM AUTHOR]

Timely and proper backfilling of open-pits in strip coal-mines has been an effective measurement for the recovery of the hydrothermal regimes and ecological environment in permafrost regions. In this study, numerical simulations and statistical regressions were applied for analyzing the recovery processes of the backfill and its major influencing factors for the thermal equilibrium in recently backfilled open pits at the Gulian strip coalmine in Mo'he, Northeast China. Results show that the thermal recovery time of backfilled areas is positively correlated to the backfill depth (BD) of the soils, the backfilled soil temperature (BST), and the mean annual ground surface temperature (MAGST); meanwhile, climate warming can impact on thermal regimes of the backfill area. The impact of climate warming on ground temperature of the backfill will show up significantly in about 50 years after backfilling (BD at 10.0 and 20.0 m, BST at 20.0°C) under the climate warming scenario (CWS) of 0.025°C·year−1. Grey-relation analyses show that the sensitivity of the backfill recovery time declines in the order of the BD, BST and MAGST. On the basis of the abovementioned studies, the layer-by-layer backfilling in cold seasons is advised for more effective and more rapid recovery of thermal regimes of the backfilled open-pits in cold regions. [ABSTRACT FROM AUTHOR]

The aim of the study is to explore roles of microRNA (miR)-124a and miR-30d in breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 144 cases of confirmed diagnosed BC with T2DM, T2DM, BC, or healthy people were enrolled. Among them, BC patients with T2DM were regarded as the experiment group ( n = 36), patients with T2DM as the Dm group ( n = 36), patients with BC as the Bc group ( n = 36), and healthy subjects as the healthy group ( n = 36). The fasting insulin resistance index, glycosylated hemoglobin, and estradiol were measured. MiR-124a and miR-30d expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The insulin resistance index was significantly higher in the experiment group compared to the other three groups (all P < 0.05). The glycated hemoglobin was in a normal range in the Bc group and healthy group, but was higher in the experiment group and the Bc group compared to that in the healthy group (both P < 0.05). The serum estradiol level was obviously higher in the Bc group compared with that in the Dm group and the experiment group (both P < 0.05). The expressions of miR-124a and miR-30d were positively correlated with insulin resistance index, BMI and glycosylated hemoglobin (miR-124a r = 0.659, r = 0.785, and r = 0.862; miR-30d r = 0.742, r = 0.805, r = 0.765; all P < 0.001). Insulin resistance index was an independent factor for expressions of miR124-a and miR-30d. MiR-124a and miR-30d were correlated with insulin resistance and development of BC with T2DM. Although the mechanism is not clear, miR-124a and miR-30d potentially may be used as therapeutic targets and prognostic markers for BC patients with T2DM. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the platelet-to-lymphocyte ratio (PLR) could be used to predict the prognosis of patients with nasopharyngeal carcinoma (NPC). Patients ( n = 1261) who were diagnosed with nonmetastatic NPC between January 2008 and December 2010 were recruited. The peripheral platelet and lymphocyte counts were retrieved, and the PLR was calculated. Univariate and multivariate Cox proportional hazards analyses were used to assess their association with PLR: overall survival (OS), cancer-specific survival (CSS), and distant metastasis-free survival (DMFS). The elevated PLR, using the third quartile values (153.64) as the optimal cutoff values, was found to be associated with the significant decline in CSS (hazard ratio [HR] 1.83, 95 % confidence interval [CI] 1.27-2.63, P < 0.001), OS (HR 1.81, 95 % CI 1.28-2.56, P < 0.001), and DMFS (HR 1.60, 95 % CI 1.15-2.23, P = 0.005) that remained significant during the multivariable analyses (CCS HR 1.84, 95 % CI 1.26-2.67, P < 0.001; OS HR 1.83, 95 % CI 1.28-2.61, P < 0.001; DMFS HR 1.56, 95 % CI 1.11-2.19, P = 0.011). Subgroup analyses indicated that the PLR could be used to stratify prognosis effectively for patients with early- or advanced-stage NPC, and Epstein-Barr virus DNA levels of ≥1500 copies/mL. In conclusions, elevated PLR values were associated with poor CSS, OS, and DMFS for patients with NPC; this easily accessed variable based on a large amount of cases multivariate analysis is valuable for predicting prognosis in patients with NPC. [ABSTRACT FROM AUTHOR]

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Recently, the Sn-Zn family of alloys, which possesses many attractive advantages such as relatively low melting point, cheap cost and the environmentally friendly component of Zn, has been widely used in electronic industry as one of the most potential replacements for the traditional Sn-Pb solders. However, there're still some arguments on its shortcomings about the poor wettability and the weak oxidation resistance, which definitely limits its further application in lead-free electronic manufacturing. In order to overcome these disadvantages and further enhance the properties of Sn-Zn lead-free solders, alloying elements such as RE, Bi, Ag, Al, Ga, Cu, etc. were selected by lots of researchers as alloys addition into the solders. This paper summarizes the effects of alloying elements on the wettability, oxidation resistance, mechanical properties and microstructures of Sn-Zn lead-free solder alloys. [ABSTRACT FROM AUTHOR]

Insulin sensitivity is decreased by prostaglandin E (PGE), a major product of cyclooxygenase (COX). As shown in erythrocytes, PGE formation is inhibited by annexin A7. The present study defined the role of annexin A7 in glucose metabolism. Gene-targeted mice lacking annexin A7 ( annexin7) were compared to wild-type mice ( annexin7). The serum 6-Keto-prostaglandin-Fα (6-Keto-PGFα) concentration was measured by ELISA and hepatic COX activity determined by an enzyme assay. Expression of COX-1, COX-2, prostaglandin E synthase, GLUT-4, and insulin receptor was determined by Western blotting. Glucose and insulin serum concentrations were analyzed following an intraperitoneal glucose load and glucose serum levels after intraperitoneal injection of insulin. Experiments were done without and with pretreatment of the mice with COX-inhibitor aspirin. The serum 6-Keto-PGFα level and hepatic COX activity were significantly higher in annexin7 than in annexin7 mice. Hepatic COX-1 expression was higher in annexin7 mice. Glucose tolerance was decreased in annexin7 mice. Intraperitoneal insulin injection decreased the serum glucose level in both genotypes, an effect significantly less pronounced in annexin7 mice. Glucose-induced insulin secretion was higher in annexin7 mice. GLUT-4 expression in skeletal muscle from annexin7 mice was reduced. Aspirin pretreatment lowered the increase in insulin concentration following glucose injection in both genotypes and virtually abrogated the differences in serum insulin between the genotypes. Aspirin pretreatment improved glucose tolerance in annexin7 mice. In conclusion, annexin A7 influences insulin sensitivity of cellular glucose uptake and thus glucose tolerance. These effects depend on COX activity. [ABSTRACT FROM AUTHOR]

An inherited predisposition to acute myeloid leukaemia (AML) is exceedingly rare, but the investigation of these families will aid in the delineation of the underlying mechanisms of the more common, sporadic cases. Three AML predisposition genes, RUNX1, CEBPA and GATA2, have been recognised, but the culprit genes in the majority of AML pedigrees remain obscure. We applied a combined strategy of linkage analysis and next-generation sequencing (NGS) technology in an autosomal-dominant AML Chinese family with 11 cases in four generations. A genome-wide linkage scan using a 500K SNP genotyping array was conducted to identify a previously unreported candidate region on 20p13 with a maximum multipoint heterogeneity LOD (HLOD) score of 3.56 (P=0.00005). Targeted NGS within this region and whole-exome sequencing (WES) revealed a missense mutation in TGM6 (RefSeq, NM_198994.2:c.1550T>G, p.(L517W)), which cosegregated with the phenotype in this family, and was absent in 530 healthy controls. The mutated amino acid was located in a highly conserved position, which may be deleterious and affect the activation of TGM6. Our results strongly support the candidacy of TGM6 as a novel familial AML-associated gene. [ABSTRACT FROM AUTHOR]

This work was focused on the influence of Ga on the thermal properties, microstructural evolution and interfacial morphology with aging treatment at 150 °C of low-silver Sn-0.5Ag-0.7Cu (SAC) lead-free solder. The melting temperature of the SAC-Ga solder was decreased owing to the low melting point element Ga and the formations of intermetallic compound (IMC) and growth at the interfaces of SAC/Cu and SAC-0.5Ga/Cu were studied for different aging time ranging from 0 to 720 h. The results indicated that for both solders, the thickness of the IMC increased with aging time prolonging. However, compared with the interface of SAC/Cu, the thickness of the interface of SAC-Ga/Cu was obviously suppressed and the growing speed was slowed down, which may be attributed to the decreased activity of copper atoms by Ga addition, so that the SAC-Ga solder showed relatively planar-like IMC instead of scallop-like at the interface. [ABSTRACT FROM AUTHOR]

The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK is a powerful regulator of ion transport. The study explored whether SPAK similarly regulates nutrient transporters, such as the Na-coupled glucose transporter SGLT1 (SLC5A1). To this end, SGLT1 was expressed in Xenopus oocytes with or without additional expression of wild-type SPAK, constitutively active SPAK, WNK-insensitive SPAK or catalytically inactive SPAK, and electrogenic glucose transport determined by dual-electrode voltage-clamp experiments. Moreover, Ussing chamber was employed to determine the electrogenic glucose transport in intestine from wild-type mice ( spak) and from gene-targeted mice carrying WNK-insensitive SPAK ( spak). In SGLT1-expressing oocytes, but not in water-injected oocytes, the glucose-dependent current ( I) was significantly decreased following coexpression of wild-type SPAK and SPAK, but not by coexpression of SPAK or SPAK. Kinetic analysis revealed that SPAK decreased maximal I without significantly modifying the glucose concentration required for halfmaximal I ( K). According to the chemiluminescence experiments, wild-type SPAK but not SPAK decreased SGLT1 protein abundance in the cell membrane. Inhibition of SGLT1 insertion by brefeldin A (5 μM) resulted in a decline of I, which was similar in the absence and presence of SPAK, suggesting that SPAK did not accelerate the retrieval of SGLT1 protein from the cell membrane but rather down-regulated carrier insertion into the cell membrane. Intestinal electrogenic glucose transport was significantly lower in spak than in spak mice. In conclusion, SPAK is a powerful negative regulator of SGLT1 protein abundance in the cell membrane and thus of electrogenic glucose transport. [ABSTRACT FROM AUTHOR]

Janus kinase 3 (JAK3) contributes to cytokine receptor signaling, confers cell survival and stimulates cell proliferation. The gain of function mutation JAK3 is found in acute megakaryoplastic leukemia. Replacement of ATP coordinating lysine by alanine yields inactive JAK3. Most recent observations revealed the capacity of JAK3 to regulate ion transport. This study thus explored whether JAK3 regulates glutamate transporters EAAT1-4, carriers accomplishing transport of glutamate and aspartate in a variety of cells including intestinal cells, renal cells, glial cells, and neurons. To this end, EAAT1, 2, 3, or 4 were expressed in Xenopus oocytes with or without additional expression of mouse wild-type JAK3, constitutively active JAK3 or inactive JAK3, and electrogenic glutamate transport was determined by dual electrode voltage clamp. Moreover, Ussing chamber was employed to determine electrogenic glutamate transport in intestine from mice lacking functional JAK3 ( jak3) and from corresponding wild-type mice ( jak3). As a result, in EAAT1, 2, 3, or 4 expressing oocytes, but not in oocytes injected with water, addition of glutamate to extracellular bath generated an inward current ( I), which was significantly increased following coexpression of JAK3. I in oocytes expressing EAAT3 was further increased by JAK3 but not by JAK3. I in EAAT3 + JAK3 expressing oocytes was significantly decreased by JAK3 inhibitor WHI-P154 (22 µM). Kinetic analysis revealed that JAK3 increased maximal I and significantly reduced the glutamate concentration required for half maximal I ( K). Intestinal electrogenic glutamate transport was significantly lower in jak3 than in jak3 mice. In conclusion, JAK3 is a powerful regulator of excitatory amino acid transporter isoforms. [ABSTRACT FROM AUTHOR]

The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. Serum lipids and lipoproteins have been reported to be associated with prognosis in some cancers, but it has not been studied in metastatic NPC. The aim of this study was to evaluate whether serum lipid and lipoproteins could predict the prognosis of metastatic NPC patients. Eight hundred and seven patients with metastatic NPC were analyzed retrospectively, and the values of serum lipids and lipoproteins at baseline were retrieved. Receiver operating characteristic curve analysis and univariate and multivariate Cox proportional hazards analyses were used to evaluate the associations of serum lipids and lipoproteins with overall survival (OS). Univariate analysis revealed that higher values of baseline cholesterol (≥4.655 mmol/L), baseline high-density lipoprotein cholesterol (≥0.965 mmol/L), and baseline apolipoprotein A-I (ApoA-I) (≥1.065 g/L) were significantly associated with superior OS ( p < 0.001), respectively. Multivariate Cox proportional hazard analysis showed that higher ApoA-I level (vs. lower ApoA-I level, HR 0.64, 95 % CI 0.52-0.80, p < 0.001) was an independent protective factor against progression. In addition, higher body mass index, earlier N stages, single lesion, and absence of liver metastasis were also revealed to be independent protective factors. In conclusion, the elevated baseline ApoA-I level may predict those patients likely to have a favorable OS. [ABSTRACT FROM AUTHOR]

The effects of rare element Ga on solderability, microstructure, and mechanical properties of Sn-0.5Ag-0.7Cu lead-free solder were investigated. The experimental results show that Ga plays a positive role in improving the wettability and the microstructure of the solder. When the content of Ga is at 0.5 wt%, the grain size of the solder is smaller and the shear force is enhanced greatly. It is also found that the thickness of the IMCs at the solder/Cu interface is reduced with proper addition of Ga. The increase of mechanical properties may be related to the refining of IMCs of the solder due to Ga addition. [ABSTRACT FROM AUTHOR]

Soil nutrients are commonly heterogeneously distributed at different spatial scales. Although numerous studies have tested the effects of soil nutrient heterogeneity on growth of clonal plants producing either spreading ramets or clumping ramets, no study has examined the effects on the growth of clonal plants producing both spreading and clumping ramets and how spatial scale affects such effects. To test these effects, clones of Buchloe dactyloides, a stoloniferous clonal plant that produces both clumping and spreading ramets, were grown in six heterogeneous environments with different patch sizes and one homogeneous environment containing the same quantity of nutrients. Total biomass, total number of ramets, number of clumping ramets, number of spreading ramets, spacer length, or root:shoot ratio of the whole plants did not differ significantly among the seven treatments. However, at the patch level there were significant effects of patch size by nutrient level on biomass, number of ramets, number of spreading ramets, and number of clumping ramets, and these four variables were significantly larger in the nutrient-rich patches than in the nutrient-poor patches in the heterogeneous treatment with the largest patch size, but not in the other five heterogeneous treatments with smaller patch sizes. Neither nutrient level nor patch size significantly affected spacer length or root:shoot ratio. Based on our results, we propose that B. dactyloides can efficiently exploit nutrient-rich patches by a plastic response of clumping ramets and spreading ramets at larger spatial scales of soil heterogeneity but not at smaller ones. [ABSTRACT FROM AUTHOR]

Janus kinase-2 (JAK2), a signaling molecule mediating effects of various hormones including leptin and growth hormone, has previously been shown to modify the activity of several channels and carriers. Leptin is known to inhibit and growth hormone to stimulate epithelial Na(+) transport, effects at least partially involving regulation of the epithelial Na(+) channel ENaC. However, no published evidence is available regarding an influence of JAK2 on the activity of the epithelial Na(+) channel ENaC. In order to test whether JAK2 participates in the regulation of ENaC, cRNA encoding ENaC was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild type JAK2, gain-of-function (V617F)JAK2 or inactive (K882E)JAK2. Moreover, ENaC was expressed with or without the ENaC regulating ubiquitin ligase Nedd4-2 with or without JAK2, (V617F)JAK2 or (K882E)JAK2. ENaC was determined from amiloride (50 μM)-sensitive current (I(amil)) in dual electrode voltage clamp. Moreover, I(amil) was determined in colonic tissue utilizing Ussing chambers. As a result, the I(amil) in ENaC-expressing oocytes was significantly decreased following coexpression of JAK2 or (V617F)JAK2, but not by coexpression of (K882E)JAK2. Coexpression of JAK2 and Nedd4-2 decreased I(amil) in ENaC-expressing oocytes to a larger extent than coexpression of Nedd4-2 alone. Exposure of ENaC- and JAK2-expressing oocytes to JAK2 inhibitor AG490 (40 μM) significantly increased I(amil). In colonic epithelium, I(amil) was significantly enhanced by AG490 pretreatment (40 μM, 1 h). In conclusion, JAK2 is a powerful inhibitor of ENaC. [ABSTRACT FROM AUTHOR]

Layer-by-layer (LbL) assembled polyelectrolyte capsules have been widely studied as promising delivery systems due to their well-controlled architectures. Although their potential applications in vitro have been widely investigated, at present, it is still a challenging task to track their real-time delivery in vivo, where and how they would be located following their administration. In this work, the noninvasive magnetic resonance imaging (MRI) technique was applied to monitor the delivery of polyelectrolyte capsules in vivo, incorporating magnetite nanoparticles as imaging components. First, MRI scan was performed over 6 h after sample administration at the magnetic field of 3.0 T; magnetic capsules, both poly(allylamine hydrochloride)/poly(styrenesulfonate sodium salt)-based and poly- l-arginine hydrochloride/dextran sulfate (Parg/DS)-based, were detected mostly in the liver region, where the transverse relaxation time (T2) was shortened and hypointense images were visualized, demonstrating a contrast-enhanced MRI effect between liver and adjacent tissue. A continuous MRI scan found that the contrast-enhanced MRI effect can last up to 30 h; in the mean time, the Parg/DS-based capsules with smaller diameter were found to have a pronounced clearance effect, which resulted in a weakened MRI effect in the liver. No obvious toxicity was found in animal studies, and all mice survived after MRI scans. Histology study provided evidences to support the MRI results, and also revealed the destination of these magnetic capsules over 30 h after administration. [ABSTRACT FROM AUTHOR]

To investigate the prognostic role of major matrix metalloproteinase (MMP) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with chemoradiotherapy. Four hundred twenty-one consecutive NPC patients were prospectively recruited. Two hundred patients were randomly selected as the training cohort, and the remaining 221 patients were the validation cohort. Twelve polymorphisms in the MMP-1, 2, 3, 7, 8, and 9 genes were genotyped by ligase detection reaction-PCR. MMP-9 rs2250889 PR/RR (HR = 2.287, 95 % CI 1.400–3.735) and rs17576 RQ/QQ (HR = 2.347, 95 % CI 1.431–3.849) genotypes were significantly related with increased death risk in the training cohort. Analysis of the validation cohort confirmed these results (rs2250889: HR = 2.231, 95 % CI 1.281–3.886; rs17576: HR = 2.987, 95 % CI 1.674–5.330). Multivariate analysis showed that rs17576 (HR = 2.284, 95 % CI 1.123–4.643, P = 0.023) was still an independent prognostic factor. The MMP-9 rs17576 is a novel independent prognostic marker in patients with locoregionally advanced NPC treated with chemoradiotherapy. [ABSTRACT FROM AUTHOR]

The microstructures, mechanical properties, corrosion behaviour and biocompatibility of the Mg-Zr-Ca alloys have been investigated for potential use in orthopaedic applications. The microstructures of the alloys were examined using X-ray diffraction analysis, optical microscopy and scanning electron microscopy. The mechanical properties of Mg-Zr-Ca alloys were determined from compressive tests. The corrosion behaviour has been investigated using an immersion test and electrochemical measurement. The biocompatibility was evaluated by cell growth factor using osteoblast-like SaOS2 cell. The experimental results indicate that the hot-rolled Mg-Zr-Ca alloys exhibit much finer microstructures than the as-cast Mg-Zr-Ca alloys which show coarse microstructures. The compressive strength of the hot-rolled alloys is much higher than that of the as-cast alloys and the human bone, which would offer appropriate mechanical properties for orthopaedic applications. The corrosion resistance of the alloys can be enhanced significantly by hot-rolling process. Hot-rolled Mg-0.5Zr-1Ca alloy (wt %) exhibits the lowest corrosion rate among all alloys studied in this paper. The hot-rolled Mg-0.5Zr-1Ca and Mg-1Zr-1Ca alloys exhibit better biocompatibility than other studied alloys and possess advanced mechanical properties, corrosion resistance and biocompatibility, suggesting that they have a great potential to be good candidates for orthopaedic applications. [ABSTRACT FROM AUTHOR]

A fusion protein of single-chain, Fv-tumor necrosis factor α, scFv-TNF, was constructed and expressed in the Pichia pastoris expression system. There was 67-fold less toxicity of the fusion protein when compared with TNF-α alone in cells expressing CA125. Furthermore, scFv-TNF was 10-fold more selective in cell killing directed by anti-CA125 scFv in a CA125-positive cell line than the CA125-negative line. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a severe health threat to human beings; however, the epidemic and molecular characteristics exist along with the change in the geographic environment and genealogy. Jiangxi province is located in southeast China, which is a high-MDR-TB burden area. Rifampin (RIF) and isoniazid (INH) are the most important first-line anti-tuberculosis drugs. The major drug target genes include rpoB for RIF and katG, inhA, and ahpC for INH. To determine the frequency and distribution of mycobacterial mutations in these genes, we sequenced specific genes of M. tuberculosis that are associated with resistance to RIF and INH in 157 phenotypic MDR isolates. At the same time, RD105 DTM-PCR and 15 loci MIRU-VNTR were performed to demonstrate the genetic lineage. It was shown that the Beijing genotype was predominant (84.1%) among these strains. The results also showed mutations within the 81 bp core region of rpoB in 93.6% of strains and mutations in a structural gene (katG) and two regulatory regions (the promoter of inhA and intergenic region of oxyR-ahpC) were shown in 88.5% of phenotypic MDR isolates. There were no significant differences in codon mutations between the Beijing and non-Beijing genotypes, as well as the clustered and no-clustered strains. The most prevalent mutations involved in RIF and INH were Ser531Leu in rpoB (55.4%) and Ser315Thr in KatG (56.1%), respectively. There was no significant difference in RIF and INH resistance between MDR-TB and other drug-resistant tuberculosis (DR-TB). The results demonstrated that some MDR-TB patients are predicted to have recent transmission. [ABSTRACT FROM AUTHOR]

Circadian rhythms are orchestrated by a master clock that emerges from a network of circadian pacemaker neurons. The master clock is synchronized to external light/dark cycles through photoentrainment, but the circuit mechanisms underlying visual photoentrainment remain largely unknown. Here, we report that Drosophila has eye-mediated photoentrainment via a parallel pacemaker neuron organization. Patch-clamp recordings of central circadian pacemaker neurons reveal that light excites most of them independently of one another. We also show that light-responding pacemaker neurons send their dendrites to a neuropil called accessary medulla (aMe), where they make monosynaptic connections with Hofbauer-Buchner eyelet photoreceptors and interneurons that transmit compound-eye signals. Laser ablation of aMe and eye removal both abolish light responses of circadian pacemaker neurons, revealing aMe as a hub to channel eye inputs to central circadian clock. Taken together, we demonstrate that the central clock receives eye inputs via hub-organized parallel circuits in Drosophila. The central circadian clock in Drosophila is made up of ~ 150 anatomically distributed neurons; the circuits underlying photoentrainment is unclear. This study describes ex vivo patch-clamp recording of the eye-mediated light response of all known circadian clock neurons, and shows that they are organized in parallel circuits centered around a hub. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 31-year-old woman who underwent cesarean section due to fetal distress. An epidural anesthesia was administered with an uneventful lumbar puncture and surgery. The patient noted mild pain in the left scapular region and back post surgery. The article discusses epidural hematoma in pregnancy, its neurological symptoms and recovery, and highlights the importance of close monitoring in patients receiving patient-controlled epidural anesthesia.

Layer I neurons in the prefrontal cortex (PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors (nAChRs) increases excitatory neurotransmission in this layer. Here we found that nicotine selectively increased the amplitude of AMPA receptor (AMPAR)-mediated current and AMPA/NMDA ratio, while without effect on NMDA receptor-mediated current. The augmentation of AMPAR current by nicotine was inhibited by a selective α7-nAChR antagonist methyllycaconitine (MLA) and intracellular calcium chelator BAPTA. In addition, nicotinic effect on mEPSC or paired-pulse ratio was also prevented by MLA. Moreover, an enhanced inward rectification of AMPAR current by nicotine suggested a functional role of calcium permeable and GluA1 containing AMPAR. Consistently, nicotine enhancement of AMPAR current was inhibited by a selective calcium-permeable AMPAR inhibitor IEM-1460. Finally, the intracellular inclusion of synthetic peptide designed to block GluA1 subunit of AMPAR at CAMKII, PKC or PKA phosphorylation site, as well as corresponding kinase inhibitor, blocked nicotinic augmentation of AMPA/NMDA ratio. These results have revealed that nicotine increases AMPAR current by modulating the phosphorylation state of GluA1 which is dependent on α7-nAChR and intracellular calcium. [ABSTRACT FROM AUTHOR]