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The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.

Purpose: We propose an FDK-based neural network to directly learn the filter from an iterative reconstruction (IR) algorithm and apply the learned filter in the FDK algorithm to obtain a high-quality CBCT reconstruction. Methods: The FDK algorithm is transformed into a linear expression of several matrix multipliers and embedded into neural network layers. Then, the FDK-based neural network framework is built including two fundamental modules and four core network layers. This network model can learn a filter directly from the iteratively reconstructed CBCT images by cascading the network layers of cosine weighting, filtering, backprojection, and leaky rectified linear unit and setting filter as the only trainable parameter. Preliminary and simulation studies performed on abdominal CT datasets are conducted to explore the correctness and effectiveness of the learned filter. Then, the head and neck CT data and Catphan phantom are utilized to demonstrate the generalization performance of the learned filter. Results: Preliminary study shows that the learned filter is consistent with the target filter, and the mean absolute difference is around 0.001. Compared with conventional FDK, the FDK-based neural network shows a better image quality with the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) increasing by 67% and 6%, respectively. In terms of the line-pair slice in the Catphan phantom, the SSIM and PSNR are improved by 13.75% and 42.78%, respectively. Conclusions: The FDK-based neural network can reconstruct high-quality images by directly learning a filter from the label images and provides a new perspective on solving the time-consuming problem of IR methods.

The pathogenicity of grapevine geminivirus A (GGVA), a recently identified DNA virus, to grapevine plants remains largely unclear. Here, we report a new GGVA isolate (named GGVAQN) obtained from grapevine ‘Queen Nina’ plants with severe disease symptoms. The infectious clone of GGVAQN (pXT-GGVAQN) was constructed to investigate its pathogenicity. Nicotiana benthamiana plants inoculated with GGVAQN by agroinfiltration displayed upward leaf curling and chlorotic mottling symptoms. A simple, quick, and efficient method for delivering DNA clones of GGVAQN into grapevine plants was developed, by which Agrobacterium tumefaciens cells carrying pXT-GGVAQN were introduced into the roots of in vitro-grown ‘Red Globe’ grape plantlets with a syringe. By this method, all ‘Red Globe’ grape plants were systemically infected with GGVAQN, and the plants exhibited chlorotic mottling symptoms on their upper leaves and downward curling, interveinal yellowing, and leaf-margin necrosis symptoms on their lower leaves. Our results provide insights into the pathogenicity of GGVA and a simple and efficient inoculation method to deliver infectious viral clones to woody perennial plants.

Abstract Inspired by the successful application of the q‐Weibull distribution in other research fields, we took the lead to use it in the field of medical devices in this work. The parameter estimation of the q‐Weibull distribution was performed using the probability plot method. The CT failure data from Nanfang Hospital in Guangzhou, China, were used to study the reliability of CT equipment at two levels: the CT system and its seven main components. In terms of evaluation accuracy, the mean squared error, Akaike's information criterion, and the determination coefficient were used to compare the accuracy of fitting of different distribution models. The results show that the accuracy of fitting the q‐Weibull distribution is higher than that of the Weibull distribution in terms of determination coefficient and mean squared error. When considering the complexity of the model, the fit accuracy of the Weibull distribution is better. The results were analyzed using reliability and failure rate plots. The q‐Weibull distribution gives a good fit for the failure data of the CT system and components. Though the Weibull distribution fits better in a few cases, the q‐Weibull distribution can describe the entire “bathtub curve” with only a set of parameters. The findings of this study can be extended to other medical devices.

Abstract Background Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI. Methods In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated. Results The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues. Conclusions Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.

Context Lilium davidii var. unicolour Cotton (Lilium genus, Liliaceae) is an edible plant and a herb used in China to alleviate insomnia. Objective To investigate the alleviating insomnia mechanism of L. davidii (LD). Materials and methods Wistar rats were intraperitoneally injected with p-chlorophenylalanine (PCPA) to establish an insomnia model. Rats were divided into six groups (n = 8): Control, PCPA, Estazolam (0.5 mg/kg), LD extract in low, medium and high doses (185.22, 370.44, 740.88 mg/kg). Serum hormone levels of the HPA axis, levels of 5-HT, NE and MT, and the expression of GABAA and 5-HT1A receptors in hypothalamus were determined. Moreover, behavioural and pathological changes in the hypothalamus were evaluated. Results After LD administration, body weight and brain coefficient increased by 2.74% and 8.22%, respectively, and the adrenal coefficient decreased by 25%, compared with PCPA group. Elevation of the serum hypothalamic-pituitary-adrenal (HPA) axis hormone CRH (11.24 ± 3.16 ng/mL), ACTH (565.87 ± 103.44 pg/mL) and CORT (44.28 ± 8.73 ng/mL) in the PCPA group was reversed after LD treatment. Furthermore, abnormal excitatory behaviour [5 min movement distance (2096.34 ± 259.51 cm), central exercise time (5.28 ± 1.08 s)] of insomnia rats in the PCPA group was also relieved. LD extract increased 5-HT and MT levels, reduced NE level in the hypothalamus, and upregulated the expression of GABAA R and 5-HT1A. Moreover, LD extract may improve the pathology of neurons in the hypothalamus. Conclusions LD can be considered to develop health-care food or novel drugs to cope with the increasing number of insomniacs.

Phosphorus (P) is a key and a limiting nutrient in ecosystems and plays an important role in many physiological and biochemical processes, affecting both terrestrial ecosystem productivity and soil carbon storage. However, only a few global land surface models have incorporated P cycle and used to investigate the interactions of C-N-P and its limitation on terrestrial ecosystems. The overall objective of this study was to integrate the P cycle and its interaction with carbon (C) and nitrogen (N) into new processes model of TRIPLEX-CNP. In this study, key processes of the P cycle, including P pool sizes and fluxes in plant, litter, and soil were integrated into a new model framework, TRIPLEX-CNP. We also added dynamic P:C ratios for different ecosystems. Based on sensitivity analysis results, we identified the phosphorus resorption coefficient of leaf (rpleaf) as the most influential parameter to gross primary productivity (GPP) and biomass, and determined optimal coefficients for different plant functional types (PFTs). TRIPLEX-CNP was calibrated with 49 sites and validated against 116 sites across eight biomes globally. The results suggested that TRIPLEX-CNP performed well on simulating the global GPP and soil organic carbon (SOC) with respective R2 values of 0.85 and 0.78 (both p < 0.01) between simulated and observed values. The R2 of simulation and observation of total biomass are 0.67 (p < 0.01) by TRIPLEX-CNP. The overall model performance had been improved in global GPP, total biomass and SOC after adding the P cycle comparing with the earlier version. Our work represents the promising step toward new coupled ecosystem process models for improving the quantifications of land carbon cycle and reducing uncertainty.

Background: Systemic inflammation and severe fibrosis can reduce serum zinc levels, while zinc supplementation is reported to improve the prognosis of patients with chronic liver disease (CLD). Objectives: We aimed to investigate the clinical application of serum zinc in patients with CLD and the anti-infective mechanism of zinc supplementation. Methods: Based on the serum zinc level, 149 CLD patients were divided into 3 groups and their clinical parameters were compared. In in-vitro experiments, microbial isolates derived from patients were used to stimulate human liver non-parenchymal cells, and the zinc sulfate solution was added in certain experiments. The effect of zinc was compared by LDH and thromboxane A2 levels in the cell supernatant. Result: Compared with other groups, patients with low serum zinc levels had significantly higher C-reactive protein (CRP), total bilirubin, INR, creatinine, and MELD scores, while albumin and GOT levels were reduced. Only CRP and albumin were significantly correlated with serum zinc in both low and normal-zinc groups. Bacterial isolates significantly increased LDH levels in Kupffer cells (KCs) and stellate cells but had no effect on sinusoidal endothelial cells, whereas zinc pretreatment protected KCs but not stellate cells. Thromboxane A2 secreted by KCs can also be induced by bacterial stimulation, accompanied by increased gene expression of Myd88, MAPK and NF-kB, while zinc pretreatment can attenuate that. Conclusion: Serum zinc levels can be used to estimate infection and liver fibrosis in CLD patients. As a new antibacterial weapon, zinc supplementation acts on KCs through Myd88-MAPK related pathways.

Data about the feasibility and safety of thoracoscopic surgery under non-intubated anesthesia and regional block are limited. In this prospective study, 57 consecutive patients scheduled for thoracoscopic surgery were enrolled. Patients were sedated with dexmedetomidine and anesthetized with propofol and remifentanil. Ropivacaine was used for intercostal nerve and paravertebral block. Lidocaine was used for vagal block. The primary outcomes were mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and end-tidal carbon dioxide partial pressure (ETCO2) at T0 (pre-anesthesia), T1 (immediately after laryngeal mask/nasopharyngeal airway placement), T2 (immediately after skin incision), T3 (10 min after opening the chest), T4 (end of surgery), and T5 (immediately after laryngeal mask/nasopharyngeal airway removal). One patient required conversion to intubation, 15 developed intraoperative hypotension, and two had hypoxemia. MAP at T0 and T5 was higher than at T1–T4; MAP at T3 was lower (P

This study examines the integration experiences of mainland Chinese tertiary-level students in Finland, a non-Anglophone country. The article identifies four conceptual domains of integration – academic, social, economic and cultural – as central to the students’ integration processes. Data for analysing the Chinese students’ integration experiences were collected through semi-structured interviews (n = 30), and the research findings showed that both English and the host language Finnish mediated the Chinese students’ integration into the host academic and social environments. Although the students initially faced challenges in their studies and daily lives, many of them managed to establish meaningful cross-cultural social contact and overcame cultural differences and language barriers to integrate into the new academic environment. The findings suggest that the maintenance of transnational ties and co-national networks can facilitate Chinese international student integration abroad, through promotion of meaningful cross-cultural contacts that contribute to the host society.

This article presents an analysis of the academic integration experiences of mainland Chinese tertiary-level students in Germany. Using Tinto’s model, the article explores the challenges that Chinese students face during their academic integration, the strategies they employ, and the relationship between academic and social integration. The data were collected in spring 2016 by interviewing 26 mainland Chinese students studying either in German universities or universities of applied sciences. Four major challenges were identified and analyzed: language barrier, knowledge gap, pedagogical differences, and cultural differences. An important outcome of the study presented is that social integration serves as a facilitator for enhancing academic integration, but is not a prerequisite for academic success. Group learning with peers was found to enhance learning outcomes. Overall, Chinese students have exploited their own advantages in academic integration by exploring feasible strategies and benefiting from their past learning experiences. It is suggested that academic integration as a long and challenging process for international students should be acknowledged by the German HEIs, and that more institutional support and guidance are needed.

Introduction: Preliminary data suggested that non-invasive methods could be useful to assess presence of oesophageal varices (OV) in liver cirrhosis. The primary objectives were to investigate non-invasive markers for diagnosing and grading OV in patients with primary biliary cirrhosis. Material and methods: This study included a total of 106 consecutive treatment-naive patients with primary biliary cirrhosis (PBC). Results of physical examination, blood tests, and abdominal ultrasound scan (USS) were measured. Performance of non-invasive markers for OV was expressed as sensitivity, specificity, positive, and negative predictive values (PPV, NPV), accuracy, and area under the curve (AUC). Results: Oesophageal varices were found in 54 (50.9%) and large OV in 28 of the 106 patients. Variables found to differ significantly between patients with any grade or large and without OV included increased spleen length, increased portal vein diameter, low platelet count, and low levels of albumin or low -glutamyltranspeptidase (-GGT) values. Area under the receiver operating characteristic curve showed that spleen length (cutoff = 156.0) had AUC 0.753 (95% CI: 0.657–0.849), and high NPV (82.1%) to exclude any grade OV. Large OV could be excluded with NPV 70.6% by spleen length. Conclusions : Predictive risk factors that use readily available laboratory results and ultrasound scan results may reliably identify esophageal varices in patients with PBC.

Urban rail transit is a new type of rail transit, between railway and urban rail transit, mainly used to solve the traffic problems between cities. By using the urban functional network model, this paper analyzes the complementary coefficient changes of Guangzhou, Zhuhai and Macao before and after the completion of urban rail transit in Guangdong Province. Through quantitative data, it intuitively shows the objective changes brought by urban rail transit to urban planning and development, and also brings development space for urban tourism economy, and deepens the economic ties between cities.

The 2001–2012 MODIS MCD12Q1 land cover data and MOD17A3 NPP data were used to calculate changes in land cover in China and annual changes in net primary productivity (NPP) during a 12-year period and to quantitatively analyze the effects of land cover change on the NPP of China’s terrestrial ecosystems. The results revealed that during the study period, no changes in land cover type occurred in 7447.31 thousand km2 of China, while the area of vegetation cover increased by 160.97 thousand km2 in the rest of the country. Forest cover increased to 20.91%, which was mainly due to the conversion of large areas of savanna (345.19 thousand km2) and cropland (178.96 thousand km2) to forest. During the 12-year study period, the annual mean NPP of China was 2.70 PgC and increased by 0.25 PgC, from 2.50 to 2.75 PgC. Of this change, 0.21 PgC occurred in areas where there was no land cover change, while 0.04 PgC occurred in areas where there was land cover change. The contributions of forest and cropland to NPP exhibited increasing trends, while the contributions of shrubland and grassland to NPP decreased. Among these land cover types, the contributions of forest and cropland to the national NPP were the greatest, accounting for 40.97% and 27.95%, respectively, of the annual total NPP. There was no significant correlation between changes in forest area and changes in total annual NPP (R2 < 0.1), while the correlation coefficient for changes in cropland area and total annual NPP was 0.48. Additionally, the area of cropland converted to other land cover types was negatively correlated with the changes in NPP, and the loss of cropland caused a reduction in the national NPP.

ObjectiveThe aim of this study was to longitudinally evaluate and analyze the role of interleukin-22-producing CD4 positive cells (IL-22) in the pathogenesis of Hepatitis C Virus recurrence after Orthotopic Liver Transplantation (HCV-OLT).Methods15 HCV-OLT, 15 age- and gender- matched non-HCV post-OLT (OLT) and 15 hepatitis C virus infected (HCV) patients were enrolled into our study from the liver transplantation and research center at Beijing 302 Hospital. We determined the frequencies of IL-22 using flow cytometry and expression of IL-22 mRNA using PCR in peripheral blood and liver tissue. We also divided HCV-OLT patients into rapid fibrosis progression (RFP) and slow fibrosis progression (SFP), examined IL-22 cells and analyzed the correlations between IL-22 frequencies and liver injury, fibrosis and clinical parameters. Moreover, we investigated the role of IL-22 in Human Hepatic Stellate Cells (HSCs).ResultsThe levels of serum IL-22, frequencies of IL-22 producing cells in peripheral blood mononuclear cells, and expression of IL-22 mRNA and protein in the liver in the HCV-OLT group were significantly higher than that in the HCV and OLT groups. Furthermore, eight (53.3%) patients developed RFP after two years; another three patients were diagnosed liver cirrhosis. The frequencies of IL-22 were much higher in RFP compared with SFP, while no significant difference existed between OLT and SFP. Intrahepatic IL-22 positive cells were located in fibrotic areas and significantly correlated with α-smooth muscle actin (α-SMA) and fibrosis staging scores, not with grading scores and HCRVNA. In vitro, IL-22 administration prevented HSCs apoptosis, promoted HSCs proliferation and activation, up-regulated the expression of HSC-sourced growth factors including α-SMA, TGF-β and TIMP-1, and increased the production of liver fibrosis markers including laminin, hyaluronic acid and collagen type IV.ConclusionPeripheral and intrahepatic IL-22 is up-regulated and plays a pathological role in exacerbating liver fibrosis by activating HSCs in HCV-OLT patients, which may predict RFP and serve as an attractive target for anti-fibrotic therapy.

Computational investigations on the bisphospholanoethane (BPE)-ligated Cu-catalyzed enantioselective addition of enynes to ketones were performed with the density functional theory (DFT) method. Two BPE-mesitylcopper (CuMes) catalysts, BPE-CuMes and (S,S)-Ph-BPE–CuMes, were employed to probe the reaction mechanism with the emphasis on stereoselectivity. The calculations on the BPE-CuMes system indicate that the active metallized enyne intermediate acts as the catalyst for the catalytic cycle. The catalytic cycle involves two steps: (1) ketone addition to the alkene moiety of the metallized enyne; and (2) metallization of the enyne followed by the release of product with the recovery of the active metallized enyne intermediate. The first step accounts for the distribution of the products, and therefore is the stereo-controlling step in chiral systems. In the chiral (S,S)-Ph-BPE–CuMes system, the steric hindrance is vital for the distribution of products and responsible for the stereoselectivity of this reaction. The steric hindrance between the phenyl ring of the two substrates and groups at the chiral centers in the ligand skeleton is identified as the original of the stereoselectivity for the titled reaction.

ObjectiveTo longitudinally investigate the role of FoxP3+ Regulatory T cells (Treg) and interleukin17-producing T helper 17 cells (Th17) in De Novo Hepatitis B Virus infection after orthotopic Liver Transplantation (DNHB-OLT), and analyze the possible correlation between these cells and HBV clearance of the disease.MethodsWe enrolled 12 control cases after orthotopic Liver Transplantation (OLT) and 24 patients, including 12 diagnosed with DNHB-OLT and 12 diagnosed with Acute Hepatitis B Virus infection (AHB), into the study from the liver transplantation and research center at Beijing 302 Hospital. Flow cytometry was used to detect the frequencies of Treg and Th17, and ELISA was applied to detect the concentration of IL6, IL22, TGF-β and IL2 in peripheral blood. We also measured the gene expression level by real time-quantitative PCR and protein expression using immunohistochemistry and western-blot. Furthermore, we divided DNHB-OLT patients into the clearance and non-clearance groups and examined longitudinally Th17, Treg cells at different times.ResultsThe percentage of Treg cells, expression of FoxP3 mRNA and related anti-inflammatory cytokines such as IL2 and TGF-β1 in the DNHB-OLT group were significantly higher than that in the AHB and OLT groups. The percentage of Th17 cells, expression of RORγt mRNA and related pro-inflammatory cytokines such as IL17 and IL22 in the DNHB-OLT group were significantly lower than that in the AHB group, but the levels of these cytokines are very similar to the OLT group. The ratios of Treg to Th17 in the DNHB-OLT group were significantly higher than that in the OLT and AHB groups. Treg frequencies significantly correlated with HBV DNA, whereas IL17 frequencies didn't significantly correlate with ALT. In DNHB-OLT patients, the clearance group was accompanied by a rapid increase in the Th17 cells during the first 4th week and afterwards continuously decrease to the control group, together with a continuously decrease in Treg cells from the onset time point, which lead to a significant reduction in the ratios of Treg to Th17. The non-clearance group was accompanied by an increase in the Treg cells during the first 4th week and afterwards sharply decrease, together with a relatively stable and unchanged Th17 cells, which lead to a significant change in the ratios. In addition, compared to clearance group, the ratios of Treg to Th17 in non-clearance group were significantly higher at the onset point, 4th and 12th week, but no difference at 24th week.ConclusionDNHB-OLT patients possessed a favorable Treg differentiation environment, accompanied by a sustained higher preferentially Treg frequencies and up-regulation of related anti-inflammatory cytokines. The immune imbalance of the ratios between Treg and Th17 existed in DNHB-OLT patients. The changes of the ratios during the DNHB-OLT events were associated with HBV clearance, which suppressed immune inflammation reaction as well as inhibited ability of specific HBV clearance and led to immune escape and chronicity.

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPSinduced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels. [ABSTRACT FROM AUTHOR]