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Coal mining is the main factor causing China’s CO2 emissions. However, the composition of CO2 emissions caused by coal mining is still unclear. In this study, we developed a detection method that combines climatologically homogeneous region recognition and semiparametric regression to quantitatively calculate the contribution of human activities and climate to CO2 emissions. On the basis of determining the composition of CO2 emissions in Shanxi coalfield, we calculated the value of four CO2 emissions components (coal mining, climate, other disturbances and random fluctuation), analyzed their temporal and spatial regulation, and discussed the relationship between each component and land use. The results show that the coal mining component accounted for the largest proportion, 81 % of the CO2 emissions, and the climate component accounted for the smallest proportion. From 2000 to 2019, the CO2 emissions and coal mining component in the study area showed a trend of first increasing and then decreasing, reaching maximum monthly values of 65.5 t and 55.6 t in 2009 and declining in 2010 and 2018, respectively. The components of CO2 emissions were strongly correlated with the land cover types. Forestland had the lowest climate component (-0.35 t), as well as other disturbances component (7.37 t). Farmland had the lowest coal mining component (20.14 t). Water and built-up land had the highest value of each component. In the future, the climate component of farms in the study area will show an upward trend, while forestland, grassland and water will show a downward trend. The detection methods of CO2 emission components can be incorporated into the ecosystem model to improve the governance and protection ability of the ecological environment.

Background: Down syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level., Methods: Amniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 17 3/7 and 24 0/7  weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites., Results: Fifty differential metabolites, including L-glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS-DA model, FDR-adjusted p-value < 0.05, and |log 2 FC| > log 2 (1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS-DA model and FDR-adjusted p-value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00., Conclusions: Our results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS., (© 2024 John Wiley & Sons Ltd.)

Background: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis., Methods: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed., Results: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study., Conclusions: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes., (© Association for Diagnostics & Laboratory Medicine 2024.)

Lithium-sulfur (Li-S) batteries are one of the most promising high-energy density secondary batteries due to their high theoretical energy density of 2600 Wh kg -1 . However, the sluggish kinetics and severe "shuttle effect" of polysulfides are the well-known barriers that hinder their practical applications. A carefully designed catalytic host of sulfur may be an effective strategy that not only accelerates the conversion of polysulfides but also limit their dissolution to mitigate the "shuttle effect." Herein, in situ surface-phosphided Ni 0.96 Co 0.03 Mn 0.01 O (p-NCMO) oxide microspheres are prepared via gas-phase phosphidation as a catalytic host of sulfur. The as-prepared unique heterostructured microspheres, with enriched surface-coated metal phosphide, exhibit superior synergistic effect of catalytic conversion and absorption of the otherwise soluble intermediate polysulfides. Correspondingly, the sulfur cathode exhibits excellent electrochemical performance, including a high initial discharge capacity (1162 mAh g s -1 at 0.1C), long cycling stability (491 mAh g s -1 after 1000 cycles at 1C), and excellent rate performance (565 mAh g s -1 at 5C). Importantly, the newly prepared sulfur cathode shows a high areal capacity of 4.0 mAh cm -2 and long cycle stability under harsh conditions (high sulfur loading of 5.3 mg cm -2 and lean electrolyte/sulfur ratio of 5.8 μL mg -1 ). This work proposes an effective strategy to develop the catalytic hosts of sulfur for achieving high-performance Li-S batteries via surface phosphidation.

Nowadays, flexible multifunctional composites are attracting much attention and are practically being used in various emerging electronic devices. However, most composites suffer from the disadvantages of high loadings of conductive fillers, complicated preparation processes, and low energy conversion efficiency. In this article, Caffeic acid-modified multiwalled carbon nanotubes (C-MWCNTs)/poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid (PEDOT:PSS)/polyimide (PI) composite films (CPFs) were prepared using a simple layer-by-layer deposition method. The "reinforced concrete" structure of the C-MWCNTs/PEDOT:PSS layer ensures high electrical conductivity of the film, while the PI layer provides excellent mechanical properties (72.69 MPa). The composite film exhibits excellent electrothermal response and thermal stability up to approximately 125 °C at 5 V. In addition, the good conductivity of the film provides its electromagnetic shielding effectiveness (32.69 dB). With these advantages, we expect that flexible CPFs will be widely utilized in wearable devices, electromagnetic interference (EMI) shielding applications, and thermal management of personal or electronic devices.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment., Aim: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT)., Methods: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT., Results: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR ( P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS., Conclusion: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection., Competing Interests: Conflict-of-interest statement: The authors who have taken part in this study have nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatocellular carcinoma (HCC), the main pathological type of liver cancer, is related to risk factors such as viral hepatitis, alcohol intake, and non-alcoholic fatty liver disease (NAFLD). The constitutive activation of the PI3K/AKT signaling pathway is common in HCC and has essential involvement in tumor progression. The serine/threonine kinase AKT has several downstream substrates, which have been implicated in the regulation of cellular metabolism. However, the contribution of each of the three AKT isoforms, i.e., AKT1, AKT2 and AKT3, to HCC metabolism has not been comprehensively investigated. In this study, we analyzed the functional role of AKT1, AKT2 and AKT3 in HCC metabolism. The overexpression of activated AKT1, AKT2 and AKT3 isoforms in the human HCC cell lines Hep3B and Huh7 resulted in higher oxygen consumption rate (OCR), ATP production, maximal respiration and spare respiratory capacity in comparison to vector-transduced cells. Vice versa, lentiviral vector-mediated knockdowns of each AKT isoform reduced OCR in both cell lines. Reduced OCR rates observed in the three AKT isoform knockdowns were associated with reduced extracellular acidification rates (ECAR) and reduced lactate production in both analyzed cell lines. Mechanistically, the downregulation of OCR by AKT isoform knockdowns correlated with an increased phosphorylation of the pyruvate dehydrogenase on Ser232, which negatively regulates the activity of this crucial gatekeeper of mitochondrial respiration. In summary, our data indicate that each of the three AKT isoforms is able to upregulate OCR, ECAR and lactate production independently of each other in human HCC cells through the regulation of the pyruvate dehydrogenase.

The natural characteristics of protein/polysaccharide-based hydrogels, as a potential drug delivery platform, have attracted extensive attention. Probiotics have attracted renewed interest in drug research because of their beneficial effects on host health. The idea of using probiotics loaded on protein/polysaccharide-based hydrogels as potential drugs to treat different diseases has been put forward and shows great prospects. Based on this, in this review, we highlight the design strategy of hydrogels loaded probiotic-mediated therapy systems and review the potential diseases that have been proved to be treatable in the laboratory, including promoting wound healing and improving intestinal health and vaginal health, and discuss the challenges existing in the current design., Competing Interests: Declaration of competing interest The authors declare that they have no known competitive economic interests or personal relationships, which may affect the work reported in this review., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation., Competing Interests: LT, TW, WM, MB No competing interests declared, (© 2023, Tian et al.)

Global climate change and population growth pose a serious threat to world food security. The current crops varieties will be insufficient to meet food needs in the future, and there is an urgent need for high yielding and quality crops varieties with strong environmental adaptability. The rapid de novo domestication of wild species to create new germplasm that can be applied to crop breeding is a new strategy for ensuring food security. The flowering time is an important factor in determining the crop planting area and yield, and is a trait that is often selected in crop domestication. At present, the modification of flowering traits by de novo domestication is usually achieved by direct editing of the major genes that control flowering in crop, which are very limited in number and relatively homogeneous in function. Floral transition is regulated by the complex network of environmental and endogenous signals. Here, we propose a new strategy that using genome editing to precisely modify protein function by changing protein phase separation capacity of important proteins that regulate expression of flowering genes, which may provide new options for the design of flowering traits in de novo domestication.

Oncogenic signaling involved in tumor metabolic reprogramming. Tumorigenesis was not only determined by the mutations or deletion of oncogenes but also accompanied by the reprogramming of cellular metabolism. Metabolic alterations play a crucial regulatory role in the development and progression of tumors. Oncogenic PI3K/AKT signaling mediates the metabolic switch in cancer cells and immune cells in the tumor microenvironment. PI3K/AKT and its downstream effector branch off and connect to multiple steps of metabolism, such as glucose, lipids, and amino acids. Thus, PI3K inhibitor could effectively regulate metabolic pathway and impede the oncogenic process and some key metabolic proteins or critical enzymes also constitute biomarkers for tumor diagnosis and treatment. In the current review, we summarize the significant effect of PI3K/AKT signaling toward tumor metabolism, it enables us to obtain the better understanding for this interaction and develop more effective therapeutic strategies targeting cancer cell metabolism., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients., Methods: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared., Results: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE ( P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved ( P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar., Conclusions: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events., (© 2023 JGC All rights reserved; www.jgc301.com.)

This paper focuses on determining the authenticity and identifying the species of Fritillariae cirrhosae using electronic nose, electronic tongue, and electronic eye sensors, near infrared and mid-level data fusion. 80 batches of Fritillariae cirrhosae and its counterfeits (including several batches of Fritillaria unibracteata Hsiao et K.C. Hsia, Fritillaria przewalskii Maxim, Fritillaria delavayi Franch and Fritillaria ussuriensis Maxim) were initially identified by Chinese medicine specialists and by criteria in the 2020 edition of Chinese Pharmacopoeia . After obtaining the information from several sensors we constructed single-source PLS-DA models for authenticity identification and single-source PCA-DA models for species identification. We selected variables of interest by VIP value and Wilk's lambda value, and we subsequently constructed the three-source fusion model of intelligent senses and the four-source fusion model of intelligent senses and near-infrared spectroscopy. We then explained and analyzed the four-source fusion models based on the sensitive substances detected by key sensors. The accuracies of single-source authenticity PLS-DA identification models based on electronic nose, electronic eye, electronic tongue sensors and near-infrared were respectively 96.25%, 91.25%, 97.50% and 97.50%. The accuracies of single-source PCA-DA species identification models were respectively 85%, 71.25%, 97.50% and 97.50%. After three-source data fusion, the accuracy of the authenticity identification of the PLS-DA identification model was 97.50% and the accuracy of the species identification of the PCA-DA model was 95%. After four-source data fusion, the accuracy of the authenticity of the PLS-DA identification model was 98.75% and the accuracy of the species identification of the PCA-DA model was 97.50%. In terms of authenticity identification, four-source data fusion can improve the performance of the model, while for the identification of the species the four-source data fusion failed to optimize the performance of the model. We conclude that electronic nose, electronic tongue, electronic eye data and near-infrared spectroscopy combined with data fusion and chemometrics methods can identify the authenticity and determine the species of Fritillariae cirrhosae . Our model explanation and analysis can help other researchers identify key quality factors for sample identification. This study aims to provide a reference method for the quality evaluation of Chinese herbs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gui, Li, Ma, Tian, Hou, Li, Fan, Wang, Yao, Shi, Zhang, Li and Liu.)

Ceftriaxone is widely used in children with community-acquired pneumonia. Currently, there are no available data regarding epithelial lining fluid (ELF) concentrations of ceftriaxone in children. Thus, blood and bronchoalveolar lavage fluids samples were collected by using an opportunistic sampling design, then we determined plasma and ELF concentrations in 22 children (0.5-11.7 years), with a total of 36 plasma and 22 ELF samples available for analysis. Ceftriaxone plasma and ELF concentrations ranged from 1.07 to 138.71 mg/L and from 0.61 to 26.69 mg/L, respectively. Ceftriaxone concentration in ELF was 12.18 ± 5.15 (mean ± standard deviation) times higher than that in plasma, ranging from 1.29 to 20.44., (© 2022 The British Pharmacological Society.)

Fusarium concentricum Nirenberg & O' Donnell (Ascomycota: Hypocreales) is a fungal species known to infect plants, but never reported as entomopathogenic. Polychrosis cunninhamiacola Liu et Pei (Lepidoptera: Tortricidae: Olethreutinae) is a major and widespread insect pest causing economic losses to cultivated Chinese fir Cunninghamia lanceolata (Lamb.) Hook. It is routinely controlled by extensive use of chemical insecticides, which is perceived as environmentally unsustainable. During March and April of 2019-2020, muscardine cadavers of larvae and pupae of P. cunninhamiacola infected with growing fungus were collected in a fir forest in northern Guangdong Province, China. Conidia were isolated and cultured on PDA medium, from which the fungal strain was identified as F. concentricum FCPC-L01 by morphology and by sequence alignment match with Tef-1α gene. Pathogenicity bioassays at the conidial concentration 1 × 107 revealed P. cunninhamiacola adults and Danaus chrysippus (L.) (Lepidoptera: Nymphalidae) larvae are sensitive to the fungal infection, but not the fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae). We believe results indicate this fungal strain might be applicable against specific target insect pests. As this is the first record of a natural infection caused by F. concentricum in insects, we propose host specificity tests should be done to evaluate its potential as a biocontrol agent., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI., (© 2023. The Author(s).)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.

Objective: To investigate the difference in clinical efficacy between zero-profile interbody fusion (ROI-C) and stand-alone interbody cage combined with cage-titanium plate construct for patient with two-segment skipped cervical spondylosis who received the anterior cervical discectomy and fusion (ACDF) surgical strategies. Methods: The clinical data of 62 patients with two-segment skipped cervical spondylosis who underwent surgical treatment in the First Affiliated Hospital of Zhengzhou University from June 2017 to June 2020 were retrospectively analyzed, included 38 males and 24 females, aged (53.3±8.5) years. Thirty-three cases were treated with ROI-C (ROI-C group), and 29 cases with stand-alone interbody cage combined with cage-titanium plate construct (cage+titanium plate group). The following parameters, including operation time, intraoperative blood loss, dysphagia Bazaz grade, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) of pain, neck disability index (NDI), average intervertebral height of operated segments, C 2-7 Cobb angle, and related complications, were compared between the two groups. Results: The patients were followed up for (28±5) months (16-34 months). The operation time of ROI-C group was (127.6±34.2) min, which was shorter than that in cage+titanium plate group [(157.1±43.9) min, P =0.004]. The scores of JOA and VAS in both ROI-C group and cage+titanium plate group were significantly improved 3 months after operation when compared with those before operation, and there was no significant difference between the two groups (all P >0.05). The average intervertebral space height of fusion segment in ROI-C group was (6.02±1.03) mm before operation, it was improved to (8.38±1.47) mm at 3 months after operation, (8.16±1.40) mm at 12 months after operation, and it was (6.24±1.05) mm, (8.58±1.18) mm and (7.87±0.73) mm in cage+titanium plate group, respectively, and there was no significant difference between the two groups at each time point (all P >0.05). The Cobb angle of cervical vertebrae in ROI-C group was 10.5°±6.8° before operation, improved to 19.2°±9.0° at 3 months after operation, 18.2°±5.8° at 12 months after operation, and it was 10.9°±4.6°, 18.5°±7.8°, 17.1°±5.2° in cage+titanium plate group, respectively, and there was no significant difference between the two groups at each time point (all P >0.05). The incidence of postoperative dysphagia was 9.1%(3/33) in the ROI-C group and 37.9%(11/29) in the cage+titanium plate group, and the difference was statistically significant ( P =0.007). Conclusions: Both ROI-C and stand-alone interbody cage combined with cage-titanium plate construct can achieve good results for two-segment skipped cervical spondylosis. However, ROI-C is more advantageous in shortening the operation time and reducing early postoperative dysphagia.

Mitochondrion, as the main energy-supply organelle, is the key target region that determines neuronal survival and death during ischemia. When an ischemic stroke occurs, timely removal of damaged mitochondria is very important for improving mitochondrial function and repairing nerve damage. This study investigated the effect of ligustilide(LIG), an active ingredient of Chinese medicine, on mitochondrial function and mitophagy based on the oxygen and glucose deprivation/reperfusion(OGD/R)-induced injury model in HT22 cells. By OGD/R-induced injury model was induced in vitro, HT22 cells were pre-treated with LIG for 3 h, and the cell viability was detected by the CCK-8 assay. Immunofluorescence and flow cytometry were used to detect indicators related to mitochondrial function, such as mitochondrial membrane potential, calcium overload, and reactive oxygen species(ROS). Western blot was used to detect the expression of dynamin-related protein 1(Drp1, mitochondrial fission protein) and cleaved caspase-3(apoptotic protein). Immunofluorescence was used to observe the co-localization of the translocase of outer mitochondrial membrane 20(TOMM20, mitochondrial marker) and lysosome-associated membrane protein 2(LAMP2, autophagy marker). The results showed that LIG increased the cell viability of HT22 cells as compared with the conditions in the model group. Furthermore, LIG also inhibited the ROS release, calcium overload, and the decrease in mitochondrial membrane potential in HT22 cells after OGD/R-induced injury, facilitated Drp1 expression, and promoted the co-localization of TOMM20 and LAMP2. The findings indicate that LIG can improve the mitochondrial function after OGD/R-induced injury and promote mitophagy. When mitophagy inhibitor mdivi-1 was administered, the expression of apoptotic protein increased, suggesting that the neuroprotective effect of LIG may be related to the promotion of mitophagy.

Vibrio alginolyticus is a halophilic organism usually found in marine environments. It has attracted attention as an opportunistic pathogen of aquatic animals and humans, but there are very few reports on polyhydroxyalkanoate (PHA) production using V. alginolyticus as the host. In this study, two V. alginolyticus strains, LHF01 and LHF02, isolated from water samples collected from salt fields were found to produce poly(3-hydroxybutyrate) (PHB) from a variety of sugars and organic acids. Glycerol was the best carbon source and yielded the highest PHB titer in both strains. Further optimization of the NaCl concentration and culture temperature improved the PHB titer from 1.87 to 5.08 g/L in V. alginolyticus LHF01. In addition, the use of propionate as a secondary carbon source resulted in the production of poly(3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV). V. alginolyticus LHF01 may be a promising host for PHA production using cheap waste glycerol from biodiesel refining.

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56 bri CD16 - natural killer (NK) cells and upregulation of interferon-gamma in effector CD4 + and CD8 + T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4 + T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections., (© 2021. The Author(s).)

Background: The management of severe extravasation injuries is still controversial. Extravasation injuries can be treated in many ways., Aim: To present a series of patients with severe extravasation injuries due to infusion who were managed with ethacridine lactate dressing combined with localized closure and phototherapy., Methods: In this study, we evaluated the data of eight patients, including six from the Department of Burn, one (with colorectal carcinoma) from the Veteran Cadre Department, and one (with leukemia) from the Hematology Department. Of these, three patients were male and five were female. Age of the patients ranged from 10 mo to 72 years, including two children (10 and 19 mo of age). In this study, the infusion was stopped immediately when the extravasation was identified. The extravasation event was managed routinely using a blocking solution. A ring-shaped localized closure was performed using the blocking agents. Moreover, ethacridine lactate dressing and phototherapy were applied for 3-5 d., Results: In this study, the drugs contained in the infusates were iodixanol, norepinephrine, alprostadil, amino acids, fat emulsion, cefoselis, cefoxitin, and potassium chloride + concentrated sodium chloride. All of the patients achieved complete healing after treatment and no obvious adverse reactions were observed., Conclusion: The treatment of severe extravasation injuries using a combination of localized closure, ethacridine lactate dressing, and phototherapy resulted in satisfactory outcomes in patients., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocalizations. Here, we demonstrate that Bengalese finches ( Lonchura striata domestica ), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. 'ab-c' versus 'ab-d') in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech., Competing Interests: LV, LT, CM, MB No competing interests declared, (© 2021, Veit et al.)

Amoxicillin is used to treat various bacterial infections (eg, pneumonia, sepsis, meningitis) in infants. Despite its frequent use, there is a lack of population pharmacokinetic studies in infants, resulting in a substantial variability in dosing regimens used in clinical practice. Therefore, the objective of this study was to evaluate the population pharmacokinetics of intravenous amoxicillin in infants and suggest an optimal dosage regimen. Blood samples were collected for the determination of amoxicillin concentrations using an opportunistic sampling strategy. The amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 62 pharmacokinetic samples from 47 infants (age range, 0.09 to 2.0 years) were available for analysis. A 2-compartment model with first-order elimination was most suitable to describe the population pharmacokinetics of amoxicillin, and covariate analysis showed that only current body weight was a significant covariate. Monte Carlo simulation demonstrated that the currently used dosage regimen (25 mg/kg twice daily) resulted in only 22.4% of infants reaching their pharmacodynamic target, using a minimum inhibitory concentration (MIC) break point of 2 mg/L, whereas a dosage regimen (60 mg/kg thrice daily), as supported by the British National Formulary for Children, resulted in 80.9% of infants achieving their pharmacodynamic target. It is recommended to change antibiotics for infections caused by Escherichia coli (MIC = 8.0 mg/L) because only 27.9% of infants reached target using 60 mg/kg thrice daily., (© 2020, The American College of Clinical Pharmacology.)

α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, BsAbfA, was cloned from Bacilus subtilis, and its codons were optimized for efficient expression in E. coli BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization. Site-directed mutagenesis of BsAbfA was performed to verify the catalytic site, and the molecular mechanism of BsAbfA catalyzing ginsenoside Rc was analyzed by molecular docking, using the homology model of sequence alignment with other β-glycosidases. The results show that the purified BsAbfA had a specific activity of 32.6 U/mg. Under optimal conditions (pH 5, 40 °C), the kinetic parameters K m of BsAbfA for p NP-α-Araf and ginsenoside Rc were 0.6 mM and 0.4 mM, while the K cat /K m were 181.5 s -1 mM -1 and 197.8 s -1 mM -1 , respectively. More than 90% of ginsenoside Rc could be transformed by 12 U/mL purified BsAbfA at 40 °C and pH 5 in 24 h. The results of molecular docking and site-directed mutagenesis suggested that the E173 and E292 variants for BsAbfA are important in recognizing ginsenoside Rc effectively, and to make it enter the active pocket to hydrolyze the outer arabinofuranosyl moieties at C 20 position. These remarkable properties and the catalytic mechanism of BsAbfA provide a good alternative for the effective biotransformation of the major ginsenoside Rc into Rd.

Tetragonal ([Formula: see text]) FeNi is a promising material for high-performance rare-earth-free permanent magnets. Pure tetragonal FeNi is very difficult to synthesize due to its low chemical order-disorder transition temperature ([Formula: see text] K), and thus one must consider alternative non-equilibrium processing routes and alloy design strategies that make the formation of tetragonal FeNi feasible. In this paper, we investigate by density functional theory as implemented in the exact muffin-tin orbitals method whether alloying FeNi with a suitable element can have a positive impact on the phase formation and ordering properties while largely maintaining its attractive intrinsic magnetic properties. We find that small amount of non-magnetic (Al and Ti) or magnetic (Cr and Co) elements increase the order-disorder transition temperature. Adding Mo to the Co-doped system further enhances the ordering temperature while the Curie temperature is decreased only by a few degrees. Our results show that alloying is a viable route to stabilizing the ordered tetragonal phase of FeNi.

Seven entomopathogenic fungi strains (M1-7) were isolated from field-obtained dead coconut hispine beetles Brontispa longissima (Gestro), identified to species, and bioassayed for their pathogenicity. According to ITS sequences, all isolates belong in the genus Metarhizium, mainly M. flavoviride and M. anisopliae. Measured median lethal times (LT50) of 1×107 conidia/ml of M1-7 against fourth-instar B. longissima larvae within 15 d following exposure were, respectively: 5.43, 10.64, 11.26, 10.93, 6.62, 4.73, and 5.95 d. The isolate M6 yielded the highest mortality to fourth-instar larvae, and was thus selected to be tested against other larval instars and adults of B. longissima, after Time-Dose-Mortality (TDM) models. M6 proved more pathogenic against larvae than adults. The obtained bioassays data produced a good fit to the TDM models, yielding estimated LC50 and LT50 for each of the tested developmental stages of B. longissima. Both the obtained dose (β) and time effect (ri) parameters from TDM models suggest that first-instar larvae are the most susceptible life stage of the pest insect, while adults are more resistant to M6 infection. Calculated LC50 values were, respectively, 1.23×103 and 1.15×106 conidia/ml for first-instar larvae and adults, on the 15th day following M6 inoculation. Estimated LT50 were 3.3 and 5.9 d for first-instar larvae and adults, respectively, at 1×108 conidia/ml. Taken together, these results would suggest Metarhizium M6 as an option for the biological control of B. longissima in the field., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Spiders can produce up to seven different types of silks or glues with different mechanical properties. Of these, flagelliform (Flag) silk is the most elastic, and aciniform (AcSp1) silk is the toughest. To produce a chimeric spider silk (spidroin) Flag R -AcSp1 R , we fused one repetitive module of flagelliform silk from Araneus ventricosus and one repetitive module of aciniform silk from Argiope trifasciata. The recombinant protein expressed in E. coli formed silk-like fibers by manual-drawing. CD analysis showed that the secondary structure of Flag R -AcSp1 R spidroin remained stable during the gradual reduction of pH from 7.0 to 5.5. The spectrum of FTIR indicated that the secondary structure of Flag R -AcSp1 R changed from α-helix to β-sheet. The conformation change of Flag R -AcSp1 R was similar to other spidroins in the fiber formation process. SEM analysis revealed that the mean diameter of the fibers was around 1 ~ 2 μm, and the surface was smooth and uniform. The chimeric fibers exhibited superior toughness (~33.1 MJ/m 3 ) and tensile strength (~261.4 MPa). This study provides new insight into design of chimeric spider silks with high mechanical properties., (© 2020 Wiley Periodicals LLC.)

Background: Sonneratia apetala Francis Buchanan-Hamilton (Sonneratiaceae, Myrtales), is a woody species with high adaptability and seed production capacity. S. apetala is widely cultivated worldwide as the main species for mangrove construction. However, the study of diseases affecting S. apetala is limitted, with only a few fungal pathogens being recorded. Cryphonectriaceae (Diaporthales) species are the main pathogens of plants. They can cause canker diseases to several trees and thereby seriously threaten the health of the hosts. These pathogens include Cryphonectria parasitica (Cryphonectriaceae) causing chestnut blight on Castanea (Rigling and Prospero 2017) and Cytospora chrysosperma (Cytosporaceae) causing polar and willow canker to Populus and Salix (Wang et al. 2015) . Therefore, the timely detection of of Cryphonectriaceae canker pathogens on S. apetala is extremely important for protecting the mangrove forests., New Information: Two diaporthalean fungi, Celoporthe guangdongensis and Cytospora rhizophorae have been reported for the first time to cause canker on the branches of S. apetala . C. guangdongensis is significantly pathogenic and C. rhizophorae is saprophytic on S. apetala ., (Long yan Tian, Jin zhu Xu, Dan yang Zhao, Hua long Qiu, Hua Yang, Chang sheng Qin.)

Purpose: To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen., Methods: From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained., Results: The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L)., Conclusion: Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.

Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT >MIC ), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics., (Copyright © 2020 American Society for Microbiology.)

The ordered phase of the FeNi system is known for its promising magnetic properties that make it a first-class rare-earth free permanent magnet. Mapping out the parameter space controlling the order-disorder transformation is an important step towards finding growth conditions that stabilize the [Formula: see text] phase of FeNi. In this work, we study the magnetic properties and chemical order-disorder transformation in FeNi as a function of lattice expansion by utilizing ab initio alloy theory. The largest volume expansion considered here is 29% which corresponds to a pressure of [Formula: see text] GPa. The thermodynamic and magnetic calculations are formulated in terms of a long-range order parameter, which is subsequently used to find the ordering temperature as a function of pressure. We show that negative pressure promotes ordering, meaning that synthetic routes involving an increase of the volume of FeNi are expected to expand the stability field of the [Formula: see text] phase.

Background: The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation., Methods: Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation., Results: The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated., Conclusions: Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.

Flaccidoside II (FLA II), the primary active constituent from Anemone flaccida rhizome, was proven to exert therapeutic effect against collagen-induced arthritis (CIA). In this study, a research based on the CIA mouse model was carried out in order to elucidate its therapeutic mechanisms preliminarily. The mice were immunized with porcine type-II collagen to induce CIA and administrated intragastrically with FLA II daily from day 7-42 of the first collagen immunization. The arthritis scores as reflected by the severity of paw swelling and erythema were significantly reduced in FLA II (32 mg/kg) from day 33 onwards. On day 42, the joints of FLA II-treated mice exhibited obvious reductions of inflammatory cells infiltration, synovial hyperplasia and bone destruction. When the concentration of FLA II was no less than 40 nmol/ml, the treatment notably inhibited T and B lymphocyte proliferative responses. As compared to the model group, in FLA II groups, the serum levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were significantly decreased while those of Th2 type cytokines (IL-4 and IL-10) were clearly enhanced. In addition, FLA II treatment showed little regulatory effect on the levels of Th1 type cytokines (IFN-γ and IL-2). The severity of mice CIA was improved by FLA II, further confirming its potential value for the safe treatment of rheumatoid arthritis. The main mechanisms likely involve the inhibition of lymphocyte proliferation and pro-inflammatory cytokine secretion, and the modulation of Th1/Th2-related cytokine balance in CIA., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The quality of traditional Chinese medicine tablets is correlated with clinical efficacy and drug safety, and plays a great role in promoting the development of traditional Chinese medicine. However, the existing traditional artificial identification and modern instrument detection in terms of accuracy and timeliness have both advantages and disadvantages. Therefore, how to quickly and accurately identify the quality of traditional Chinese medicine tablets has become a high-profile issue. The purpose of this paper is to explore the feasibility of the application of electronic eye technology in the study of rapid identification of traditional Chinese medicine quality. A total of 80 batches of samples were collected and tested by Fritillariae Cirrhosae Bulbus for traditional empirical identification(M&#95;1) and modern pharmacopeia(M&#95;2). The optical data was collected from electronic eyes, and the chemical metrology was used to establish suitable discrimination models(M&#95;3). Four authenticity and commodity specification models, namely identification analysis(DA), minimum bidirectional support vector machine(LS-SVM), partial minimum two-multiplier analysis(PLS-DA), main component analysis identification analysis(PCA-DA), were established, respectively. The accuracies of the authenticity identification models were 82.5%, 90.0%, 96.2% and 93.8%, while the accuracies of the commodity specification identification models were 89.3%, 96.0%, 90.7% and 97.3%, respectively. The models were well judged, the authenticity identification was based on the final identification model of PLS-DA, and the commodity specification was based on the final identification model of PCA-DA. There was no significant difference between its accuracy and M&#95;1, and the time of determination was much shorter than M&#95;2(P&lt;0.01). Therefore, electronic-eye technology could be used for the rapid identification of the quality of Fritillariae Cirrhosae Bulbus.

Background: This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-ICC)., Patients and Methods: The density of tumor-infiltrating CD3 + , CD8 + , CD163 + , and Foxp3 + immune cells, as well as Programmed cell death 1, Programmed cell death-ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC-ICC by immunohistochemistry. The immune index was established to stratify patients. Prognostic significance of immune cell subsets and immune indices was evaluated., Results: The distribution of immune cells was highly heterogeneous among different subregions of cHCC-ICC. As compared with the hepatocellular carcinoma (HCC) component, the lower density of CD8 + T cells and higher intensity of Foxp3 + Tregs and immune checkpoints in the intrahepatic cholangiocarcinoma (ICC) component may indicate a stronger immune evasive ability of ICC. Based on clustering classification or a combination of random forest and lasso-cox, two models of immune indices were established and both were identified as independent prognostic factors for cHCC-ICC patients. The selected immune variables in the immune prognostic models derived from both HCC and ICC subregions, indicating that the prognosis of cHCC-ICC patients was a complex interaction of both components., Conclusions: The immune contexture was heterogeneous among different subregions of cHCC-ICC patients and contributed differently to patient prognosis. Immune score based on the densities of immune cells might serve as a promising prognostic predictor for cHCC-ICC patients., (© 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objective: To systematically evaluate the efficacy of pressure therapy in treating patients with hypertrophic scars by meta-analysis. Methods: Databases including PubMed, Embase, Web of Science, and Cochrane Library were retrieved with the search terms"hypertrophic scar, hyperplastic scar, HTS, pressure therapy, pressure treatment, and the Chinese Journals Full - text Database was retrieved with the search terms in Chinese version",,,,"to obtain the publicly published randomized controlled trials about pressure therapy in the treatment of patients with hypertrophic scar from the establishment of each database to July 2017. The measurement indexes included the effective ratio, Vancouver Scar Scale (VSS) score, scar vascularity, scar hardness, scar pigment, scar thickness, and value of scar color (brightness, red, and yellow). RevMan 5.3 and Stata 12.0 statistical software were used to conduct a meta-analysis of eligible studies. Results: A total of 667 hypertrophic scar patients were enrolled in 11 articles, including 362 patients in pressure therapy group who received pressure treatment and 305 patients in untreated group who received no treatment. The bias risks of the 11 studies included were uncertain. Compared with those of untreated group, the effective ratio of patients in pressure therapy group was significantly increased, with the relative risk of 5.98 (95% confidence interval=1.83-19.46, P <0.01); the VSS score and scar vascularity of patients in pressure therapy group were obviously decreased, with weighted mean differences of -2.24 and -0.66 respectively (95% confidence interval=-4.16--0.33, -1.21--0.12, P <0.05); the scar hardness, scar pigment, scar thickness, and value of scar color (brightness, red, and yellow) of patients in pressure therapy group were not changed obviously ( P ≥0.05). Significant heterogeneity existed in the included studies of the effective ratio, VSS score, scar vascularity, scar hardness, scar pigment, and scar thickness, P <0.01, I (2)=90%, 87%, 80%, 93%, 86%, 94%. Pressure range might be the heterogeneity source of effective ratio, and pressure clothing combined with pressure pad therapy might be a heterogeneous source of VSS score. Sensitivity analysis showed that the combined effect size results were stable in the effective ratio and scar pigment, but not stable in the VSS score, scar thickness, scar hardness, and scar vascularity. There was no publication bias in the effective ratio, VSS score, scar hardness, scar pigment, and scar vascularity ( P >0.1), while there was publication bias in the scar thickness (95% confidence interval=-19.77--3.30, P <0.1). Conclusions: Compared with patients without treatment, in the treatment of hypertrophic scars, pressure therapy can obviously increase the effective ratio, reduce the VSS score and scar vascularity, but can not obviously improve the scar hardness, scar pigment, scar thickness, and value of scar color (brightness, red, and yellow).

The development of electronic technology has attracted attention on the biological effects of electromagnetic fields (EMFs) and electromagnetic pulse (EMP). It remains controversial whether EMP irradiation is neurotoxic or beneficial for recovery from injuryies such as cerebral ischemia. Microglia is innate immune cells in the brain, exhibiting either neurotoxicity or neuroprotection effect during various central nervous system diseases, depending on their activation into a classical (M1) or alternative (M2) phenotype, respectively. The Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NFκB) pathway is important for microglia activation. In this study, we investigated the effect of EMP on neuronal apoptosis and microglia polarization in vivo and in vitro, using an EMP of 400 kV/m and 1 hertz for 200 pulses. Short EMP irradiation (≤24 h) resulted in microglial conversion from the resting to the M1-type state, activation of the TLR4/MyD88/NFκB pathway, higher levels of inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor-α, as well as neuronal apoptosis induction. In contrast, long EMP irradiation (3 days) resulted in microglial activation into the M2-type, decreased apoptosis and inflammatory mediator production, and increased levels of the neuroprotective effectors IL-10, transforming growth factor beta, and brain-derived neurotrophic factor. EMP induces both neuronal damage and neuronal recovery by influencing the switch of M1/M2 polarization and the TLR4/MyD88/NFκB pathway., (Copyright 2019 Biolife Sas. www.biolifesas.org.)

The thermodynamic ordering transformation of tetragonal FeNi system is investigated by the Exact Muffin-Tin Orbitals (EMTO) method. The tetragonal distortion of the unit cell is taken into account and the free energy is calculated as a function of long-range order and includes the configurational, vibrational, electronic and magnetic contributions. We find that both configurational and vibrational effects are important and that the vibrational effect lowers the predicted transformation temperature by about 480 K compared to the value obtained merely from the configurational free energy. The predicted temperature is in excellent agreement with the experimental value when all contributions are taken into account. We also perform spin dynamics calculations for the magnetic transition temperature and find it to be in agreement with the experiments. The present research opens new opportunities for quantum-mechanical engineering of the chemical and magnetic ordering in tetrataenite.

Background: For emergency department (ED) patients, risk assessment, prophylaxis, early diagnosis and appropriate treatment of venous thromboembolism (VTE) are essential for preventing morbidity and mortality. This study aimes to investigate knowledge amongst emergency medical staff in the management of VTE., Methods: We designed a questionnaire based on multiple scales. The questionnaire was distributed to the medical and nursing clinical staff in the large urban ED of a medical center in Northern China. Data was described with percentages and the Kruskal-Wallis test was used to compare ranked data between different groups. The statistical analysis was done using the SPSS 22.0 software., Results: In this survey, 180 questionnaires were distributed and 174 valid responses (response rate of 96.67%) were collected and analyzed. In scores of VTE knowledge, no significant differences were found with respect to job (doctor vs. nurse), the number of years working in clinical medicine, education level, and current position, previous hospital experience and nurses' current work location within the ED. However, in pair wise comparison, we found participants who worked in ED for more than 5 years ( n =83) scored significantly higher on the questionnaire than those under 5 years ( n =91) (95.75 vs. 79.97, P =0.039). There was a significant difference in some questions based on gender, age, job, and nurse work location, number of working years, education level, and different ED working lifetime., Conclusion: Our survey has shown deficiencies among ED medical staff in knowledge and awareness of the management of VTE. We recommend several changes be considered, such as the introduction of an interdisciplinary workshop for medical staff; the introduction of a standardized VTE protocol; a mandatory study module on VTE for new physicians and nurses; the introduction of a mandatory reporting system for adverse events (including VTE)., Competing Interests: Conflicts of interest: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Two-dimensional (2D) nanochannel arrays are constructed by bottom-up reassembly of montmorillonite monolayers that are obtained by liquid-phase exfoliation of its layered crystals, and the as-constructed interstitial space between these monolayers is uniform and provides ions with nanoscale transport channels. Surface-charge-controlled ion transport behavior is observed through these nanochannels as the electrolyte concentration reduces to 10 -4 M at room temperature. Furthermore, the nanochannel structure remains even after 400 °C heat treatment, and nanofluidic devices based on the annealed nanochannel arrays still exhibit surface-charge-governed ion transport at low electrolyte concentrations. In addition, a drift-diffusion experiment is conducted to investigate the mobility ratio of cations/anions through the nanochannels with asymmetric bulk electrolyte concentrations, and the results show that the mobility of cations is about eight to nine times that of anions, which is consistent with the fact that the montmorillonite monolayers are negatively charged and the nanochannels are permselective. Last, ionic current rectification is observed in the nanofluidic system of asymmetric geometric shape, and rectification factors of ∼2.6 and ∼3.5 can be obtained in KCl and HCl electrolytes, respectively, at a bias between -1 and +1 V because of the asymmetric electrostatic potential through the nanochannels.

Background: Radiomics is an emerging field in oncological research. In this study, we aimed at developing a radiomics score (rad-score) to estimate postoperative recurrence and survival in patients with solitary hepatocellular carcinoma (HCC)., Methods: A total of 319 solitary HCC patients (training cohort: n = 212; validation cohort: n = 107) were enrolled. Radiomics features were extracted from the artery phase of preoperatively acquired computed tomography (CT) in all patients. A rad-score was generated by using the least absolute shrinkage and selection operator (lasso) logistic model. Kaplan-Meier and Cox's hazard regression analyses were used to evaluate the prognostic significance of the rad-score. Final nomograms predicting recurrence and survival of solitary HCC patients were established based on the rad-score and clinicopathological factors. C-index and calibration statistics were used to assess the performance of nomograms., Results: Six potential radiomics features were selected out of 110 texture features to formulate the rad-score. Low rad-score positively correlated with aggressive tumor phenotypes, like larger tumor size and vascular invasion. Meanwhile, low rad-score was significantly associated with increased recurrence and reduced survival. In addition, multivariate analysis identified the rad-score as an independent prognostic factor (recurrence: Hazard ratio (HR): 2.472, 95% confident interval (CI): 1.339-4.564, p = 0.004;survival: HR: 1.558, 95%CI: 1.022-2.375, p = 0.039). Notably, the nomogram integrating rad-score had a better prognostic performance as compared with traditional staging systems. These results were further confirmed in the validation cohort., Conclusions: The preoperative CT image based rad-score was an independent prognostic factor for the postoperative outcome of solitary HCC patients. This score may be complementary to the current staging system and help to stratify individualized treatments for solitary HCC patients.

Ceftazidime, a third-generation cephalosporin, can be used for the treatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data are limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and to define the appropriate dose to optimize ceftazidime treatment. Blood samples were collected from children treated with ceftazidime, and concentrations of the drug were quantified by high-performance liquid chromatography with UV detection (HPLC-UV). A population pharmacokinetic analysis was performed using NONMEM software ( version 7.2.0). Fifty-one infants ( age range, 0.1 to 2.0 years ) were included. Sparse pharmacokinetic samples ( n = 90 ) were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight and creatinine clearance (CL CR ) were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mg / kg twice daily was associated with a high risk of underdosing in infants. In order to reach the target of 70% of the time that the free antimicrobial drug concentration exceeds the MIC ( fT >MIC ), 25 mg/kg every 8 h (q8h) and 50 mg/kg q8h were required for MICs of 4 and 8 mg/liter, respectively. The population pharmacokinetic characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation., (Copyright © 2018 American Society for Microbiology.)

This study examines the interaction between hERG and Kv4.3. The functional interaction between hERG and Kv4.3, expressed in a heterologous cell line, was studied using patch clamp techniques, western blot, immunofluorescence, and co-immunoprecipitation. Co-expression of Kv4.3 with hERG increased hERG current density (tail current after a step to +10 mV: 26 ± 3 versus 56 ± 7 pA/pF, p < 0.01). Kv4.3 co-expression also increased the protein expression and promoted the membrane localization of hERG. Western blot showed Kv4.3 increased hERG expression by Hsp70. hERG and Kv4.3 co-localized and co-immunoprecipitated in cultured 293 T cells, indicating physical interactions between hERG and Kv4.3 proteins in vitro. In addition, Hsp70 interacted with hERG and Kv4.3 respectively, and formed complexes with hERG and Kv4.3. The α subunit of I to Kv4.3 can interact with and modify the localization of the α subunit of I Kr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.

Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of "syllables." We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR) and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a "self-rescuing" feedback response to neuronal loss after sepsis., Competing Interests: None declared

The pharmacological activities of natural glycosides are closely related to the polyfunctional sugar moieties. Modification of active natural products by glycosylation can change the stereochemical configuration, improve the solubility, tune up the activities and change pharmacokinetic properties for higher efficacy and better selectivity. Compared with the common D-glucose, D-allose, a C-3 epimer of D-glucose rarely exists in nature, but it plays an important role in food, health, medicine, and so on. It is not easily metabolized in the living organisms, but can be used as a safe and low-calorie sweetener. The natural allopyranosides are absolute conjugation forms which are same as other glucopyranosides and rhamnopyranosides with a broad array of biological activities. This article summarizes the major progresses made in phytochemistry and biological activity studies of these compounds. Structure-activity relationship analyses of partial anti-tumor and anti-diabetic allopyranosides were performed regarding the data reported in the literatures. These insights may provide a theoretical and experimental reference for the discovery of new drug and drug design based on allopyranosides.

Semilocal density functional approximations occupy the second rung of the Jacob's ladder model and are thus expected to have certain limits to their applicability. A recent study [Y. Zhang, G. Kresse, and C. Wolverton, Phys. Rev. Lett. 112, 075502 (2014)] hypothesizes that the formation energy, being one of the key quantities in alloy theory, would be beyond the grasp of semilocal density functional theory (DFT). Here, we explore the physics of semilocal DFT formation energies and shed light on the connection between the accuracy of the formation energy and the ability of a semilocal approximation to produce accurate lattice constants. We demonstrate that semilocal functionals designed to perform well for alloy constituents can concomitantly solve the problem of alloy formation energies.